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Dendritic bundles: Survey of anatomical experiments and physiological theories
225
f3rain Research Reviews, 1 (1979) 225-271
DENDRITIC BUNDLES: SURVEY OF ANATOMICAL PHYSIOLOGICAL THEORIES
EXPERIMENTS
KATHLEEN
L. SHAW
J. RONEY, ARNOLD
3. SCHEIBEL*
and GORDON
AND
Department of Physics, University of CalifortGa, Irvine, Calif. 92717 and (A.B.S.) Departments of Anatomy and Psychiatry and the Brain Research Institute, U.C.L.A. Center for the Health Sciences, Los Angeles, Catif 90024 (U.S.A.) (Accepted May 11th, 1979)
Kq
wor&:
dendrites
-
mammalian
brain
-
dendritic
bundles
-
Golgi
studies
LIST OF CONTENTS
.
I. Introduction
. . . . . . . .
2. Anatomical experiments . , 2.1. Spinal cord . . . . 2.2. Brain stem . . . . 2.3. Other areas . . . . 2.4. Cerebral cortex . 2.4.1. Apical dendritic 2.4.2. Basilar dendritic 2.5. Comparisons . .
. . . . . .
.
. . . , . . .
Acknowledgements References
.
. . , . . .
.
. . . , .
228
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I
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. .
. . . .
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, , .
. . . . . . , . . . . . . . . . . .
225
228
. . .
.
3. Physiological models . . . . . . . . . . . . 3.1. Columns . . . . . . , . . . . , . 4. Summary
.
.
. . . . . . . . .
.
. .
. . . .
bundling bundling
. . . . . . . . . . .
f .
249 252 253 256 261 262
.
263 263
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261
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268
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268
1. INTRODUCTION Dendritic bundles (or clusters), which have been found throughout the mammalian brain, are unquestionably important, fundamental units involved in the brain’s functioning. However, no physiological experiments to determine their role have been performed on these well-established anatomical units! The purpose of this paper is to survey the numerous anatomical reports of bundling. We summarize the results in
* To whom correspondence
should be addressed.
226
Tables I through IV which we hope will be useful for those planning future anatomical and/or physiological experiments as well as for model builders. For illustrative purposes, we briefly discuss several physiological possibilities for the functional significance of bundles. Dendritic bundling does not necessarily have a single function but could serve in a variety of ways in different regions of the brain, e.g. as an electrophysiological unit involved in processing, as a mechanism of synchronization among neurons, as a metabolic transfer mechanism involved in neuronal maintenance, as a developmental unit important to brain growth, and 50 on. We briefly discuss a theory in which the bundles have the first-mentioned function, i.e. they act together as processing units. Very brief allusions to dendrite bundles were made by Cajal at the beginning of this century in the visual cortex’” (see also Fig. 388 of ref. IO) and by Laruelle (as noted by Barron”) in the spinal cord. These observations were forgotten, and it was not until 1970 that dendritic bundling was studied in detail. Recently, modified Golgi stains and a number of other techniques have been employed (see Table IV) which reveal a larger number of the neurons present in a region and thus enable the observation of the striking features of dendritic bundling. Dendritic bundles are groupings of dendrites which course along very closely together (typically, from 1 pm apart to direct membrane apposition) in the brain. They are a relatively general feature of the mammalian brain, having been found by many groups in the spinal cord, brain stem, cerebral cortex, nucleus reticularis thalami. habenular nucleus, and olfactory bulb. Most bundle complexes include IO-20 dendrites (with wide variation), with a bundle diameter of roughly 50 /tm and a distance between the bundles of the order of 50 pm. Thus, bundles ate not columns (see later discussion on columns) but are much smaller units. There have been many anatomical studies of bundling but, to our knowledge, no electrophysiological investigation. The importance of examining bundles electrophysiologically (and otherwise) is seen in their possible roles which are important to brain function, as follows.
(A)
Maintenance of the circulation of neuronal firing activity It has been estimated that upon the presentation of a ‘meaningful’ stimulus, a
network of neurons maintains related reverberatory firing activity for approximately I secso. Lorente de No*4 long ago realized that activity in short, simple circuits of neurons could not persist for such a long period (compared to the several msec associated with the recovery time after neuronal firing). Hebb recognized the difficulties in functionally linking in a simple circuit the large number of neurons necessary to account for the reverberatory time. Accordingly, he suggested that the firing activity of a network moves from one unit to another, for perhaps 1 sec. Bundles of dendrites could conceivably act as Hebb’s functional units. (Bj
Stability
against local brain damage
The individual neuron in a network cannot be the fundamental
element in
227 storing
information
local damage as is provided
as many neurons
die at random
and are not replaced.
should not destroy the stored information, by an assembly
(or bundle)
(C) Statistical reliabilit?’ It is known9,r6J*~sg,g0
that, although
to one stimulus
to an animal
presentation
some ‘back-up’
As limited system such
is necessary.
the spike trainresponse is not reproducible,
a single neuron to many presentations (the post-stimulus cible. However, since behavioral correlates are repeatable
of a singleneuron
the average response
of
histogram, PSH) is reprodufor a single presentation of a
stimulus, we expect that the firing response of some appropriate set of neurons is also repeatable. It has been suggested ss,79 that the spike train response to a single stimulus presentation averaged across many neurons in an assembly is the same as the PSH (determined by averaging the responses from many (~20) presentations of the same stimulus) of a single neuron in that assembly. This hypothesis defines the assembly as a localized group of neurons assemblies.
obeying this averaging.
Perhaps bundles are these theoretical
(D) Insurance of a reasonable memory storage capacity A theory developed by Shaw and Little 4a,4s,7s,st involving a network of neurons having Hebb-type modifiable synapses so showed the storage capacity to be related to the number of synapses. This result implied that the network can be excited into many different time sequences of firing patterns of assemblies of neurons (defined by the relationship in (C)), possibly bundles.
(E) Synchronization function Bundles could perhaps rather than having a processing
(F) Non-electrical
provide
a means
of synchronization
among
neurons,
function.
functions
Other possible roles of bundles in the nervous metabolic functions.
system include developmental
and
Bundling may have any of these functions or serve several purposes in different the brain. One very interesting possible function of bundling in the reticular suggested by Scheibel et al.63 and now with some experimental support, is role of programming location for ‘rhythmic repetitive output’ such as respithe rest-activity cycle. In the widest sense, dendritic bundling could act as a
regions of formation, that of the ration and
possible basis for coded memory output patterns (see refs. 71 and 73). In the study of the reticular formation of the cat, they find a progressive loss of spines and formation of dendritic bundles in the normal course of development in the kitten. Of enormous interest are the preliminary results of Quattrochi et al.s8 who have found that in Sudden Death Syndrome infants, bundling of the dendrites has not taken place and there is no apparent loss of spines. In control studies of infants of similar age dying of
228 ‘other causes’, however, the loss of spines and formation of bundles has occurred just as in the young cats. We feel that it is of the utmost importance that appropriate physiological experiments be done in order to determine the functional role or roles that these wellestablished, well-studied anatomical bundles of dendrites play in brain function. 2. ANATOMICAL
EXPERIMENTS
In this section we summarize the results of neuroanatomical work by many groups on dendrite bundles in the spinal cord, brain stem, nucleus reticularis thalami, olfactory bulb, habenular nucleus, and cerebral cortex of various mammals. We present the authors’ work, including their suggestions as to the possible functions of bundling. The information is presented in more detail in Tables I through 1V. The various staining techniques used are included in Table IV, and it must be understood that these techniques differ to some extent in the degree of their quantitative rigor. 2. I.
Spinal
cord
The lumbosacral ventral horn (lamina IX) of the spinal cord has been shown to be a site of rostrocaudal dendritic bundling in the monkeyes, cat12J5~~8Jji~68,pig”“. and ratl~~~*~~.The number of dendrites found per bundle varies, generally in the range 5-20, although in the rat the number is found to be of the order of 1200-1600 dendrites1s4’. A bundle gains and loses dendrites along its length. It is estimated68 that 80 % of the dendrites in the region form into bundles. Individual dendrites of a neuron may enter into different bundles, and dendrites from neurons in separate motor cell columns can be in the same bundle6*. The characteristic size of a bundle in this region of the spinal cord appears to be several millimeters in length68, with a diameter of the order of 50 pm, again excepting the large rat bundles found by Anderson et al.1 (maximum -1000 pm diameter) and Kerns and Peter?’ (250 pm in diameter). The distance between the dendrites in a bundle is generally reported as 2 ,um or less with some separations unresolvable by light microscopy68. Matthew et a1.48,using electron microscopy, observe some separations of 0.2-0.5 pm (Fig. I) and occasional direct apposition of membranes, including both unspecialized contact and those with electron opaque material present. Anderson, also using electron microscopy, found desmosomal dendrodendritic contacts amongst the bundled dendrites. An interesting occurrence in this regions4 is that spinal catecholamine nerve terminals from locus coeruleus, after being lesioned with 6-hydroxydopamine intracisternally, regenerate ‘as if growth was guided by the longitudinally running dendritic bundles of the motorneurons’. The ScheibeW.88 have suggested that the role of dendritic bundles in lamina IX of the lumbosacral spinal cord is to serve as a source for the program governing reciproval activity of muscle pairs in the hind limb in walking, stepping, and SO on. In support of this hypothesis is the developmental pattern of the bundles in this regions7
229 (Fig, 2). The bundles are not present at birth but develop (in the kitten) near the end of the second week, corresponding to the time when the kitten starts using its hind limbs for weight bearing and walking. By the fourth or fifth month the bundles appear fully developed and the complete repertoire of hind limb behavior has been achieved. Electromyograms
recorded
agonist-antagonist
at parallel
times show that reciprocal
activity
between
an
muscle pair is absent at birth, begins to appear at 12-14 days and is
fully developed
by the fourth
or fifth month.
Anderson
et a1.l doubt
this role of
bundling, stating that the sixth lumbar segment (where bundling was found in the rat) is only minimally involved in hind limb control. Matthews et al.48 have suggested synchronization of neuronal firing as the function of bundles in this region, based on the closeness of the dendrites involved in a bundle. Weak electrical facilitation is known to exist between cat spinal cord neurons 53; Matthews believes this might be made possible
by the contacts
al.s4,s5, however,
occurring
think there is not enough
between
dendrites
direct apposition
in a bundle. of dendritic
Sotelo
et
membranes
to consider ephaptic interaction possible. Dendritic bundles have also been found in the ventral horn of the cervical and ventroenlargement of the spinal cord of the cat69, especially in the ventromedial lateral areas. In this region the bundles are present at birth; their length increases with age (at 3-4 days, 50-100 pm; at 12-l 4 days, 150-200 pm). The region is responsible for forelimb muscle control, particularly in the proximal portions of the limb. It is hypothesized that the dendritic bundles are the storage sites for programming the reciprocal activity of muscle pairs in the forelimb for, for example, the treading reflex in the suckling kitten. The Scheibels72 have found dendritic bundles running perpendicularly to the rostrocaudal axis in the ventral commissure of both cervical and lumbosacral segments of the spinal cord of the cat (Fig. 3). Here, dendrites from both motoneurons and interneurons appear to be involved in the bundling, with up to lo-15 dendrites per bundle. A bundle may include dendrites from both medial and lateral motoneuron pools representing cells supplying muscles with both agonist and antagonist functions. Contralateral
motoneurons
lose dendrites
along its length of 100-500 pm. Also, individual
may extend into different with light microscopy
may be involved. bundles.
among
Again,
the bundle
is seen to gain and
dendrites
And as in other cases, no separation
many
of the dendrites.
These bundles
of a single cell is resolvable are present
at
birth. As the commissure in the cervical (lumbosacral) segment is responsible for coordination of arm (leg) movement, it is suggested 72 that the bundles could serve as program sites for ‘reflexive response sequences involving pairs of extremities, such as stepping and walking.’ Bundles have been found by several investigators in the ventral horn of the cervical12, thoracic12,2s and sacralla portions of the spinal cord of the cat as well as in the lateral motor nucleus of the cervical spinal cord of the fetal mousega. Bundles are possibly present (although the authors did not so state) in the intermediolateral nucleus of the thoracic spinal cord of the cat60 and in the anterior horn of the cervical spinal cord of the ratgs.
.
.fkatures o/’ dendrite
:
Motoneurons (mainly) f interneurons Motoneurons
Motoneurons
“* Dendrite3
Bundle
Bundle
Several mm
length
Largest 910 jtm
250 jrm
1200. -1600
Over 1400
2.4mm
jrm --
20.6Ojlm
IO-70 jtm (cat)
diamerer
55-85
-807:
-_
enter. bundle
up to 12
5-20(tertiary and secondary dendrites mainly. occasionally primary) 4ormoreper area 25 pm *. 25 jirn
Motoneurons
per bundle
per bundle
3-25 (cat)
NO. neurons
No. dendrites
Motoneurons
Type of neurotr
bundles
5 Lamina 1X of L7, St, SZ, Ss segments of spinal cord of pig4’ Motoneurons 6 (Ventrolateral) ventral horn of lumbar (Ltl) spinal fusiform cord of rat (2 groups of bundles : (I ) lateral and (2) medial, running perpendicularly)r Motoncurons 7 (Ventrolateral) ventral horn of lumbar (La) spinal cord of rat (also bundles in ventromedial and dorsolateral regions of ventral horn, but bundlessmaller)J’
3. Ventral horn (lamina VII, VIIIandIX)ofC2-Cs,Tr, Ja, TIN, L1-L7, SJ, s2 segments of spinal cord of cat (lamina 1X only in enlarpments)12 3 Lumbosacral spinal cord (motor nudei) of cat45
1. Ventral horn of lumbosacral spinal cord of cat and monkeys7.6s 2. Lanka IX of LR,L7.S segments of spinal cord of Lx@
Spinol cord
Area
Quonrirative
TABLE I
Dendrite
5 7.5
jlm
diameter
Mean: 2 jcm (0.2-4jdm) 88 y/, have
Ave. 1.7 jim
7- 14 jrm
Variow
.--
diameter
of dendrite
.-
Ave. : 63 pm
IOO-several hundred jlrn
Ave. : 400-600j~mtin WO-700 jtms7
while in bundle
Length
!
I
I i
I
i
I I
i !
/
1
I I
of
dendrites)
(apical
Layer V pyramidal
(apical
monkey”” Area 17, visual cortcy ~,f
rat20
13
areas 4, 17, 7
25. Visual
of rat”’
cortexg5
cortex
macaque
and 40 of human and
24. Brodman’s
of rhesus
Motor
V medium
dendrites)
dendrites)
dendrites)
Q 5 (iowcr laqcl-
dendrites)
Vb) - 7.5 (uppe1laver Va)
--
V cells, catj
2-3 (from layer
rabbit)
layer V cells,
(cat) - 5 (from
Layer Vpyramidal
dendrites)
below)
(apical
(apical
Pyramidal
(apical
Pyramidal
(apical
and large pyramidal
Layer
(presumably)
V pyramical
Layer
Layer V pyramidal (apical dendrites)
to 50
areas; (gurus genualis)
2 (striate see
rabbit)
- 15 (total,
dcndritez)
(apical
22
cortex
layer
rabbit)
h 6(in IV,
layer IV cells)
(
layer V
seeing dendrite bundles) Motor cortex of cat2*“*” i
to assume’
Large
pyramidal
21.
‘reasonable
20. Somatosensory cortex of rat*6,*7 (not definite, but
cat alone?l
19. Visual cortex of rabbit and ofcat”, rabbit alone’“*d”,
cat,
alone*+I”~37
rabbit
alonezl
cortex and catZs,2”.‘J,
rabbit
18. Somatosensory
dendrires per bundle
3-4 2-3to5-7
‘Majorit),’ (rabbit)
IX-35
,I,“,
layer Ill)
2 4ttm(in
layer V)
4 b/cm(in
min.
3 5j/rn
-..
.--.
ratT6
Pyramidaf (apical dendrites) Layer V pyramidal (apical dendrites) Layer V pyramidal ( +- layer 1V cetk. in area parietalis) (apical dendrites) Layer Vpyramidal (apicoi dendrites) Layer V pyramidal (apical dendrites)
Layer V pyramidal @pica!. dendrites)
Layer V pyramidal (apical dendrites)
Layer V pyramidal (apical dendrites)
Layer V pyramidal (apical dendrites)
35. Visual cortex of human fe- Neurohlasls tal brain (34-month-old)1~ 36. Corlical plateofIate(l%lMature ncurobiasts day) fetal rat cortexs~ Pyramidal 37. Dorsal developing neo(apical dendrites) cortex of&day-ald rat embryo, transpl~l~tcd~nto
albino
33. Barrel field, parietal cortex, striate region in mouse2s 34. Sensorimotorcnrtex of
32. Barrel field and ruea parictalis ot mouset3
3). Barrel field of mousers
28. Cortex of frontal pole, area t ofSS cortex, auditory cortex, primary visual cortex of macaquer’ 29. Cortex of frontal pole, SS and auditory cortices, primary visual cortex of humanr7 30. Opossum neocortexr7
26. Krieg areas 2, 3 (SS cortex) 4,17 (visual),41 (auditory), cortexoffrontal polc,and ‘barrel field’ of ratA7 27. Postcruciate gyrus, primary visual cortex, primary auditorycortex,SScortex, cortex offrontai pole ofcat”
-__
-
-
_l.l
--.
-
-
cells) at 36 days up to6 (from layer Vcells) at 90 days -
;
3 (from layer V --
.-
-
-
-.
-
l.l.
-
-
-
-
-
2--8 @I (areas 17, 41) 4-6 $Urn (auditory cortex) upto 1Opm (postcruciate gyrusi -
-
ss cortex: 6-8 -
I (continued) -.
41. Lateral habenular nucleus of cats’ 4’ Oval nucleus of neonatal Torpdonturmofafu(elactric Iish)midventral, rostra1 tneduIlaz5 43 Where looking: basal gangliae”.”
39. Nucleus reticularis thalami ol cat (dorsolateral zone)‘” 44-l. Olfactory bulb in adult and newborn cat73
Other
(b) Primary motor cortex of human64~7s
cerebellumof lo-day-old rat (6 days after transplant)’ 1 38. Primary motor cortex and visual cortex of (a) cat, monkey, mouse, rata? (Data applies to motor cortex)
Areu
TABLE
Small and large class
3- 4, up to Elongate IO-12 Reticularis Mitral cells (long secondary dendrites, 2-dimensional bundle in rostrccaudal plane) Medium-sized
Giant pyramidal Varies, up to 6 IO (cat) cells of Betz and large solitary cells of Meynert (layer V, basilar dendrites). (no stellate or other nonpyramidal cells contributedendrites) 3-g Giant pyramidal cells of Iktz(basilar dendrites) and V and VI layer pyramidal cells (basilar and apical dendrites)
-
‘common’
fKl 70’!,,
.__.
per bundle
_.
enter. bundle
neur*ns
dendrites per bundle
.._ --_no Dendrites
NO.
No.
._
I2 4O/cni
dicmefer
Blmdle
400-500 !rm -.
Elm
Several thousand
IenRRth
Bundle
._._
3 14/m
‘.
8/(m)
(90 0;
o/dendrite
50 jt m several hundred /lrn
_
Several mm
_. ..-
while in bundle
Length
l-3 ,ftm to -. 7-g ,drn (cat)
diameter
Dendrite
z P
3. YeritraI horn (h&xi VU, V1IlandZX)ofCz-Ce,T1, T6,“T12,L1-L7,51,520fSpinal cord ofcat (iamina IX only in enlargements)l” 4. Lumbosacral spinal cord (motor nuclei) ofcaP 5, Lamina IX of LT, SI, SZ, 5s segments of spinal cord of pip4R ‘small extracellular
-
space” -
-
Some: 0.2-Q.5 f*rn gap (separated by thin astrocyteprocesses~. Occasionat&, ptrasma rn~rn~ra~~s ii3 direct ~p~~~$~t~o~,
-
5th mo., bundles fuliy developed arid behavior compkte, Also electromyogrdms done. -
II (continued)
--
13. Brain stem reticular
core of cat (bundles beet devrl,opedinme’dial2i3 medullary and; pontine tegmentum)“!l
...-
-
_~
-...
_-..
Longest of large cells: 150@ 2oQo /Lm; of mediun~cells: 600%IOOO~rn!
19 &_.Lateral motor nucleus of C:i~~Cc segments of spina; cord of fetal mouw””
10. Ventral commissure of cervical and lumbosacral spinal cord of cat’” 11. Carnina IX of Tha-Thin segments of spinal cord o f ca~“s,zo
ofratcalso bundtesin ventromedial and dorsolateral regions of ventral horn, but bundles smaller)~’ 8. Lamina IX of cervical to ~~ lumbosacrai spinal cord of raP 9. Ventral horn of cervical enlargement of spinal cord of kittenGY
TABLE
Many Man)
01
: c I rrm : no spaceeeen
widelji’
close together
scattered
‘lying
Many : nil spaceseen withiight microscope
rcntia) More often: separated slightly by astocytic cytoplasm sheet.
-.._
-
-
but in adui:
Yet present at hicrh
Present at birth, need treading reflex of anterior extremities when kitten starts to suckle. Present al birth
~~
-
E
raphe (B /) in -mesencephalon ofsquirrel monkeyls (b) l.ocus coeruleus of squirrel monkeyIs (c) Pars compacta and pars -reticulataofsubstantia nigra, mesencephalon ofsquirrel monkeyI 1.5. Cranial nerve nucleiti3.G’ -16. Nucleus of oculomotor --nerve of catgl
-
18. Somatosensory cortex of rabbit and cat”tmz4, rabbit alone*4J”s47, cat alone”’
19. Visual cortex of rabbit -and of cat”“, rabbit aione13s r5, cat alonegl
--‘-
17. Somatosensorycortex, auditory and visuaf cortices ofratandcat(dataapplies to Krieg’s area 3 of SS cortex of ratP
Cerebral cortex
14. (a) Nucleus
0.3 pm to :.6 pm,ave.: 1.3 /tm(area parietalis, rabbit) -
-
-
-
-.
Order of 50 /dm(rabbit)
-
Some: ‘separated by the extracellular space only’
-
-50 jrm. -(Between large clusters, N 150 pm.) Since apical tufts and basilar dendrites spread N lOO~~,must intermingle with those in adjacent bundles.
-
Direct membrane apposition ‘not infrequent’ (1)12-14nm,sometimes 7-9 nm (2) Often desmosomal junctions (2530nm) (Oftenelectron-dense material)
Occasionally, ‘fairly extensive.’ Frequently, few microns.
-
-~
-
-
Columns: SI cortex,rat, .50O,~,,x diameter Auditory cortex, cat, 100fim diameter, centers separated 150 pm Visual cortex, 350&m diameter Barrels: mouse, LOO-38O~mdiameter (see ref. 55 for refs.) -
-
-
-
-
human and
W-
‘Very
often’
contact.Othcrb:
IXnm
in direct
/Irn
: 76.4/m, pheries: 53.
I /lm
between peri-
centers
Ave. between
- 80
pole,area
cortex, primary visualcorle.\ c .Y
1 of SS cortex, auditory
offrontal
offrontalpoleofcat’~
torycortex,SScortex,corte.x
audi-
gyrus, primary
visual cortex, primary
Postcruciate
cortex)
(auditory
;ortcx
of rat parictai
bundles
ship between barrelsand
50 70/m
No apparent spatial relation-
‘barrellield’ofrat17
-.
process
odor and suckling
Neonates have bundles _ relationship between
cortex of frontal pole. and
(auditory).
visual cortex)
_
Lcral microns
Sometimes
5 15nni
4,17(visua1),4i
long
30 40!cm(rat
-
-
-
Very
Krieg areas 2.3 (SS cortex).
macaque cortex”” Visual cortex ot rat”’
7 and4Oof
T
of
areas 4. 17,
17, visual cortex
Brodman’s
rat*e
Area
monkcyXn
cortex of rhesu\
Motor
ofcat’,.‘,’
cortex
bundle\)
toassume’
Motor
28. Cortex
T. i.
26.
‘reasonable
seeingdendrite
but
cortex of
rat86*s7 (not defnitc.
Somalosensory
-
35. Visual cortex of human fetal brain (34 month-old)4” 36. Cortical pfateoflatef19Zlday) fetal rat cortex56 37. Dorsal developing neocortex of 8 day-old rat embryo, transpIantedintocerebellum of 1O-day-old rat (6 days after transplant)rr 38 Primary motorcortexand visual cortex of (a) cat, monkey, mouse,rat”g (Data applies to motor cortex) (b) Primary motorcortcx of humane’.7j
-
33. Barrel field, parietal cortex, striate region in mouseaa 34. Sensorimotor cortex of albino rat76
-
Circular domain, diameter
.-
-
-
-
--
-
32. Barrel field and area parietaiis of mousetB
29. Cortex of frontal pole, SS and auditory cortices, primary visual cortex of humant? 30. Opossum neocortex17 31. Barrel field of mouse96
2 mm
-
-
IO--20 nnl, frequently nothing bctwccnmembranss
-
-
-
-
4 days after birth : loose bundle-likeorder 24 days : bundies clearly visible Number dendrites per bundle incrcascs with age (see ‘No. dendrites per bundle’)
-
-
-
-
-
-
-
-
_-
Bundle dendrites located preferentially in sides and in areas between barrels Bundle dendrites located preferentially in sides and in areas between barrels -
W
I=:
TABLE if (continued)
itlld
cat48
3. Ventral, horn (lamina VU,, VXlf and IX) of CZ-C~,TJ,TE,LI-L7, S1,Sesegments ofspinalcord ofcat (lamina IXonlyinenlarg~:rmeotsf’” 4. Lumbosacral spinal cord (motor nuclei) of cat4” 5. Lamincz IX of L7, S1, SQ, Sa segments of spinal cord of pig”* 6. (Yentralateral) ventral horn of tunbar(LI)spinalcordofrae (2 groups c&bun&s: (i j Lateral and(2) ~e~ial,ru~nin~~er~endic~~ariy~~ 7. (Ventrolatcral)ventral horn of lumbar(Le)spinalcordafrat (also bundles in ventromcdial and donolateral regionsofv~entral born, but bundlessmuIler~i~ 8. Lamina lXofcervicat to lumbosacral spina! cord of rats L
of spinal cord of
b!.Jdk
(I) Sparsity of myelinated axons in bundle region (2) ~e~drodendr~~~c contacts observed ; symmetrical electron-dcnsesubstanse present (EM) (dcstnasomal) See Area 1,Feature 2. Fewer myelinate~ axons in bundle region Dendrites occupy 55 % volume bundle neu~~p~i
-
Bundlesvery prominent in ~~r~n~cnervenucl~us and pudendal nervesand in ventral andlateralreyions of lateral motoneuronal cell group in CWTi and, somewhat, L&r ‘Might,’ be bundles
Dendritesfromcellsofdifferentmotorcell columns can be insame bundle See Area I ~feature 2
$3)
(I) Individual dendrites afsinglecell may enter different bundles (2) Bundle gainsand loses dendrites along length of
Spinal catecholamine nerve terminals from locus coeruleus after being lesioned witRO-hydroxydoGamine intracisternally, regenerate ‘as ifgrowth was guided by the longitudinally runningdendritic bundles of the nmtnneurons’.
monkey~~z6~8
2. Lamina IX of LF, L7, Sr segments
spinal cord of cat
1. Ventral born of Iumbosacral
-
No direct evidence-may of hind ~~rnb
he involved in rnove~~c~~t
‘. , . non-synaptic information transfer between neurons is predictable’. Doubtsroleincentral programmingofhind limb activity since onfy see bundles in Lc (M/hi& does not inner\iate that region much)
Synchronization _t Matthews thinks closeness of dendrites leads to synchronization of those neurons by ahering t~~res~old e~ha~t~c~I]y
‘Integrative subcenter for sphal effector activity’ Source for program for reciprocal activity of leg muscle pairs in walking, etc.
_^~
14. (a) Nucleus raphe dorsalis (B7) in mesencephalon of squirrel monkey’” (b) Locuscoerulcusofsquirrel monkey18 (c) Parscompactaand pars reticulata of substantia nigra, mesencephalon of squirrel monkeyIs 15. Cranial nerve nucleW6t
13. Brain stem reticular core ofcat (bundles best developed in medial 2/3 medullary and pon tine tegmenIumeY~)
H&n stem
segments ofspinal cordof fetal mouse(Je
12. Lateral motor nucleus of C:,--Cc
of spinal cord of cataevz9
1I, Lamina 1X ofTh~--Thl~scgmentr
10. Ventralcommissureofcervical andlumbosacralspinalcordofcatiz
9. Ventral horn ofcervical enlargement ofspinal cord of kittena
Area l..”_-... ---.I.
TABLE Xl1 (continued) _~--~X__-.--_“..~~.
~_~
(I) See Area I, Feature 2 (2) Bundles surround large fascicles ofrostrocaudal axons (3) Dendritesoften windaroundeach other, increasingchanceforcontact l3undlesinsamelocationsalsofoundinrat,cat,rabhit and rhesusandstumptail monkeystT t,using Falck .Hillarp and glyoxylicacid methods)
..--
(2) (3) (I) (2)
( I)
(2)
probably synapses Most obvious bundling in ventromedial or ventrolateral areas ofventral horn (corresponding to most proximal parts of limb) Bundles include dendrites from medial and lateral moto~uron pools. Also from agonist and antagonist function muscle motoneurons. Also fromcontralateral motoneurons. See Area 1, Feature 2 Bundles perpendicular to long axis ofcord See Area I, Feature 2 Mainly dendrites from distinct cell groups in same column, but some from other groups and from neighboring columns.
( I) Clusters of boutons frequent on or near bundles -
F%mm?s
~__ fmndh function --
Programsitesfor rhythmicrepctitiveoutput like respiration, rest--activity cycle,etc. : override control for autonomous function. Possible Sudden Infant DeathSyndrome role---Seelntroductionandref. 58.
Lack of monosynapticconnections between motoneurons in the contralateral ventral horns: doubts Scheibels’ suggested function of regulating’alternating functionsoftheextremities’ -
Program site for ‘reflexive response sequences involving pairs ofextremities, such as stepping and walking’
Program site for ‘reciprocal activity of leg muscle pairs in coordinated motor activity’
Suggested
of oculomotor
nerve
of rhesus monkeys”
23. Area 17,visual cortex of rat’” 24. Brodman’s areas 4,17,7 and 40 of humans and macaque cortex”5
22. Motor cortex
19. Visual cortex of rabbit and ofcat’“: rabbit alone1 ‘,13, cat alom+ 20. Somatosensory cortex of rat8G,8i (not definite but ‘reasonable to assume’seeing dendrite bundles) 21. Motorcortexofcat’.“.j--7
18. Somatosensory cortex of rabbit and cat?” .1-1,rabbit alonel-l.1.5,ii, cat alone”’
17. Somatosensorycortexofauditory and visual cortices of rat and cat (data applies to K&g’s area 3 of ss cortex of rat)jj
16. Nucleus of cat”’
group
-
Synchronization
Maybe
-
forms
of neurons
of bundles column
They find dendrodendritic contacts which they CI ) Neurons tend to lie beneath each other consideras basisforclcctrotonicinteraction (2) Betzcell,when present,isincentcr within a column. (3) Dendrites tend to twist around each other (4) Upper layer V and lower layer III, more dendrites join bundle (5) See Area 1, Feature 2 (6) Between dendrites, perpendicularly, run small RXCUIS forming synapses with the dendrites (7) Dendrodendritic contacts identified Associates degenerating thalamocortical terminals with bundlesin layers 1Vand 111 (quarltitativc~turly), located more frequently where more apical dendrites are. -
f I) Cell bodies grouped below dendrite bundle that bundle dendrites and neurons havecommon afferentinput since EM observations show concentration of small unmyelinated axons and terminals surrounding bundles (synapses) (3) Layer III pyramid&join bundlesfromlayer V pyramid& (I) Bundling looks different in different regions: Cat visualcortex vs rabbit or cat SS cortex (see Fig. 1I) (2) First bundling ends when dendrites bifurcate in layer Ill/l1 but canreformwithlayerIII pyramidal dendrites (3) See Area 1, Feature 2 (4) Bundle dendrites convcrgc in upper third of layer IV (rabbit) Cat visual cortex: numerous small cell processes near the bundles Bundles run from layer V 10 layer II, arborize in II, III and IV
not as ‘extensive nor so well organized’into as in other parts of brain
(2) Likely
Bundles bundles
$11 (continuedf I.-._. -_----_-._
Cortical plate of late (IV 31-da) J klal rat cortex”’ Dorsal developing ncocortcz ol !&day-old rat embryo. transplanted into cerebellum of IO-day-old rat (6 days after transplant)”
Visual torte\: clt’human fetal brain I 3. 4 month-old) ‘:I
. .-.-... -.
Ifpyramidal cells were proupcd together, their dendrites grouped into bundles. Isolated cells did not rend to habe dendrites group. So bundle formation may depend on grouping of pyramidal cells (in development) and other developmental cwnts.
-
_._ ^_.
_
cortical regions. Auditoryandvisualcorticessimilarincats. Postcruciategyrus: more dendrites(thickcr also) per bundle than auditory or visual cortex.
Bundling differs in different
_-_
Features
-....-. .1 .--~.-.
Visual cortex of rat”’ Kriegarcas 2,3 (SS cortex), 4, I7 (visual),41 (auditory),cortexof frontal pole and ‘barrel field’ of rat’? Postcruciate gyrus, primary visual cortex,primaryauditorycortex, SS cortex, cortex of frontal pole of cat” Cortexoffrontal pole,area 1 0fSS cortex,auditorycortex, primary visual cortex of macaque”. Cortex of frontal pole,% and auditorycortices, primary visual cortices, primary visual cortex of human” Opossum neocorlexli Barrel field of mouse!“’ Barrel field andarea parietali< of mouseL:) Barrel field, parietal cortex, striate region in mouse?:) Sensorimotor cortex of albino rat”’
Area
TABLE
-
Bundleslinked to formacolumn corticalaxonsanda\oncollaterals.
by \crtic‘al intra-
.-__... __-- __..I .._ .. ..._. ..I _^ .___. _~~__._. ,._ Suggested brrudfe ,fhctim
a
nuclei) of calA*
perpentlicularly)~
(I) lateral and (2) medial,
regions of ventral horn, hut hundles smallerIJ1 Lamina IX ofcervical loh~mhos;~cral \nir.al curd 01 r;il ‘.
(Ventrolatwll) ventral horn of lumbar (La) spmel cord or rat talso bundles in vcntromedial and dorsolatcral
running
~,i rat (2groupsofbundles:
5. Lamina1Xof1.7,S~.S2,S:~segments0fspinnlc0rdot‘~igi’~ hornoflumbal (Lo)
IX only in enlargemenl~)~’ 4. Lumbosacral \pinal cord (motor
IX)ofc‘~ C‘s,‘l‘l, 1‘0, 3 ventral l~orn(laminaVI‘I.VIIland 1’12,1,! I.;, S,, Sz segments of 5pm;1l chord cd cat (lamina
ca14*
hornoflumbosacralapi~lal cord ofcat and monkCyl’:.“H 2. Lamina IX IIF 1~6, L:, SI aegmcnts of spinal cord of
I. ventral
Modified Golgi
Rapid Golgi, modified
)
modification
(I’) Mallory-Heidenhain or (g) Methylene blue-azure II Uranyl acetate and lead cltrale (a) Methylcne blue or (I-P)Toluidinc blue Alcoholic uran~l acct.~tc and lcad citrate Cl-alck H~llarp :lu~~re~cer.cc histx?xx~~iatr!
tc) Luxol fast blue.-cresyl violet or Cd) Weil (for myclin sheath) or (c) Cresyl wolet (Nissl) or
Niwl -. complex ethanol ditrercntiation (a) Rapid GoI@ and Golgi C‘ox tungstate (b) Hematoxylin and eosin or
or
roluldme blue ormethylcnc blue. L‘rcs>I violet (Niwl), huffe~ed thionine. Holmcs\ilwr. or paraflin hauta or Held Auerbach Urunyl acetate and modified lcad citrate
LM
(a) 0.5 7, toluidine blue or (b) alcoholic solution of p-phenylet~cdiamine Uranyl xeta~e and lead citrate Harris hematoxylin Ponccau red lipht green
LM LM
EM
LM
TM LM
LM
Rapid Golg~, modified
-i-
cr
0
mouse”’
Barrel field, parietal cortex. striate region in mouse?:’ Sensorimotor cortex of albino ratTR Visual cortex of human fetal brain (.3 -4-month-old)‘!’ Cortical plateoflate(l921-day)fetal rat cortex””
parietalisol
zone)“’
43. Where
looking:
basal ganglia”:‘*” .._ . . _ _ ._..^, _.-._.-
.._. _
41 Lateral habenular nucleus of c&; 42. Oval nucleusofneonatal 7'urpedo/f,ar,,lurrrro (clcctriclish)midventral, rostrai medulla’j
39. Nucleus reticularis thalami of cat (dorsolatcral 40. Olfactory bulb in adult and newborn cat;,’
37. Dorsal developing neocortex of X-day-old rat embryo. transplanted intocerebellum of IO-day-old rat (6 days after transplant)” 38. Primary motor cortex and vihual cortex of (a) cat, monkey. mouse,raW (Data applies to motor cortex) (b) Primary motor cortex of hurnanb-‘,‘-
33. 34. 35. 36.
32. Barrelfieldandarea
30. Opossum neocortex17 3 1, Barrel field of mouseB’;
.________..__ “.l._
modifid
(b) Rapid Golgi, (not given)
Rapid Golgl. modllicd Rapid Golgi. modified (not given) Rapid Golgi and Gotgi- Kopsch sllvcr impregnarion methods Golgi by chloral formaldehyde procedure and toluidine blue Uran) t acetateand lead citrateand Sodium acetate bullicr and uranbl acctatc in \odium acctntc (not given) -_,___._ .._. _~
modified
Colgi,
LM 1.M EM LM LM EM
1-M EM
EM LM
LM
LM
LM
LM
Miwasrop~
1.M
-.__.
(a) Rapid
___-___
_~-~---.~______,_“~
LM EM LM EM 1.M L.rM ;Illd f PI1
_-.
(a) Toluidine hluc or (b) Nissl or (c) Cajal (not given) (a) 1 “/0 uranyl acetate in 70”, methanol or (b) Totuidine blue Lead citrate (a) Alcohol solution of toluidinc blue or (b) Hematoxylin-eosin or (c) Luxol fast blue and PAS rcactlon or (d) Bodian, modified (Luna) (not given) Gotgi-Cox (Ram&-Moliner modification) Freez-fracture,(etchingon some): then platin,~,~~--carb~~~~
(a) Toluidine blue or (b) Nissl or (c) Cajal Toluidine blue
.-
27. Postcruciategyrus, primary visual cortex, primary auditory cortex, SS cortex, cortex of frontal pole of cat’? 28. Cortex of frontal pole, area 1 of SS cortex, auditory cortex, primary visual cortex of macaque” 59. Cortex of frontal pole, SS and auditory cortices. primary visual cortex of human*i
-1 Slaining techniyue __“.
IV (continued)
Avea _._~~~~.-
I’ABLE r3 f? __
Fig. 1. Cross-section of a dendrite bundle in lamina IX of cat lu~lbosacral spinal cord. Dendrites DI and Dz are kept apart by an astroglial process Aereas Da and D.I seem directly apposed. i: 4680. (From ref. 48.)
In addition
to the spinal
cord,
dendritic
bundles
are found
in the reticular
formation of the cat”“. Bundles may include as many as 15 dendrites, with shafts joining and leaving the bundle along its length. The dendrites in bundles tend to surround large fascicles of rostrocaudal light microscopy) between the dendrites
axons. There is often no space resolvable themselves, and the separation is usually
(by less
than I /fm. Frequently, the dendrites twist around each other, making possible contact between them more likely. Bundles are not present at birth (Fig. 4). As previously noted, Scheibel et a1.63 suggest that the role of bundles in the reticular formation may be to act as a program site for ‘rhythmic repetitive output’ such as respiration and the rest-activity cycle. Bundling has been observed among the dendrites of the serotonergic cells in the nucleus raphe dorsalis, the ~loradrener~ic neurons in the locus coeruleus, and the dopaminergic cells in the pars compacta and pars reticulata of the substantia nigra of the squirrel monkey18 as well as in these locations in the rat, cat, rabbit, and rhesus and stumptail monkeys’“.
250
fetal
Id 4m
Fig. 2. Drawings of horizontal sections through the ventral horn of cat spinal cord at approximatclg LS Sl segments, showing development of motoneuron dendrites and dendrite bundles. In fetal cord, dendrites have radial distribution. At 1 day of age dendrites begin to show sagittal organization. At 12 days bundles are beginning to form at a, band c. At 4 months the motoneuron system is essentially mature and dendrite bundles at a, b and c arc well-developed. Neurons A, B and C contribute dendrites to more than one bundle. Other abbreviations: vm. ventromedial white matter: VI. ventrolateral white matter: d, a small bundle of commissural dendrites, which are apparent at even one day of age. Inset diagram shows plane of section and spinal laminar organization of the relevant area. Rapid Golgi
variant. (From ref. 74.)
251 Bundles have been identified Tredici et al.9’ in the nucleus form a hundie. separation
Direct
of the oculomotor
membrane
to desmosomai
in cranial
contacts,
apposition
nerve nuclei by Scheibel et al.64 and by nerve of the cat, where 3-5 dendrites is common,
often with electron-dense
ranging
from
material,
a 7-9 nm
of 25-30 nm
separatiorP.
Fig. 3. Drawing of horizontal section through the ventral horn of 3-month-ofd cat spinal cord at L5-Sl , showing Iongitud~naJ and horizontal dendrite bundles. A, C, E and F are rnotoneurons; B and D, spinal interneurons; a-f, dendrite bundIes crossing midfine as part ofcommissural system; g and h, ~ong~tud~nai dendrite bundles; i and j, dendrite tips protruding into ventrolateral white matter; k, tips of dendrites forming commisrural systems ending in ventral grey matter. Rapid Golgi variant. x 150. (From ref. 72.)
Fig. 4. Cross-sections through the dorsal half of the lower medulla oblongata in newborn and adult cats, showing the difference in dendrite organization of reticular neurons. In the rostra1 part of the nucleus reticularis parvocellularis, A, and the nucleus reticularis magnocellularis, B, of the newborn, neurons have radiating dendrites. In the adult, dendrites have formed bundles surrounding the rostrocaudal running fascicles of myelinated fibers. Other abbreviations: C, medial longitudinal fasciculus; D, nucleus prepositus hypoglossi; E,medial vestibular nucleus. Drawing: x 100. Rapid Golgi variant. (From ref. 74.)
2.3. Orher awas
The Scheibelsi” have found bundling in the dorsolateral zone of the nucleus reticularis thalami of the cat (Fig. 5). Here, the number of dendrites per bundle varies from 3-5 up to IO- 12, with 60-70 % of the dendrites in the area involved in bundles. The bundles gain and lose dendrites along their length of 400-500 ,um. Again, the separation between the dendrites is frequently so small as to be unresolvable by light microscopy. The bundles are not present at birth, but become progressively more obvious in the first 30-60 days of life. Because of its location, the nucleus reticularis thalami is crossed by almost all of the fibers connecting the thalamus with the cerebral cortex. There appear to be synapses between these fibers and the cells and dendrites of the nucleuss. It is thought that the nucleus serves as a feedback system, gating thalamocortical interaction by imposing tonic and/or phasic inhibition on thalamicneuronss5@j. Recent neurophysiological studies appear to support these notions”. The Scheibels suggest the bundles as possible programming sites for tuning and modulating the rhythmic slow wave processes in the thalamus and cortex.
253
Fig. 5. Drawing of horizontal section through dorsolateral portion of adult cat nucleus reticularis thalami at approximately AIO. Dendrites of many reticularis neurons (nR) form bundles (e.g. at b). Other abbreviations: f, fascicles of dorso-ventrally running axons; VB, ventrobasal nuclei; VL, ventrolateral nuclei; Cd, caudate nucleus; Hy, hypothalamus. x 300. Golgi variant. (From ref. 70.) Dendritic
bundles
the cat73. Dendrites
its course
and
are present
originating
are very tightly
in the rostrocaudal
from
the mitral
packed,
plane
of the olfactory
cells join and leave each bundle
as seen by light microscopy
bulb of along
and electron
microscopy. The bundles in the olfactory bulb are present at birth, and it is suggested that through their role as the programming site for ‘stereotyped, routine or repetitive types’ of output, the bundles are necessary in the relationship of odor to suckling behavior. Bundles have also been observed in the lateral habenular nucleus of the cats’. In animals other than mammals, bundling has been observed in fish, specifically in the oval nucleus of the neonatal Torpedo marmorata25. Close apposition of membranes (8-10 nm apart) and some desmosomal contacts (~20 nm) are commonly present. Many axodendritic synapses are observed between the bundle dendrites and the small axons that run perpendicularly to the bundles. 2.4. Cerebral cortex In the cerebral cortex two types of bundling have been found: (1) amongst the apical dendrites of layer V pyramidal cells (Figs. 6 and 7) and (2) amongst the basilar dendrites of the giant pyramidal cells of Betz and the large solitary cells of Meynert in layer V of the primary motor and visual cortices (Figs. 8 and 9).
III
Fig. 6. Drawing of four layer V pyramidal cells whose apical dendrites form a bundle. From a Colgi preparation. (From ref. 55.)
255
Fig. 7. Dendrite bundles in cat visual cortex. Top left: Frontal sections, x 200. Top right: Bottom: sagittal section showing bundle cross-sections. x 800. (From ref. 21.)
x 800.
256
Fig. 8. Comparisons of basilar dendrite patterns of medium-sized pyramids, A, in layer III with those of Betz giant pyramidal cells, B, in the fifth layer of precruciate gyrus of an adult cat. Enlargement of a bundle segment is shown at C. Rapid Golgi variant. (From ref. 74.)
2.4.1, Apical dendritic bundling
Peters and Walsh55 and Fleischhauer et al.24 were the first to report bundles formed of apical dendrites in the cerebral cortices of the rabbit, cat, and rat (Fig. 6). Peters and Walsh studied the somatosensory, auditory and visual cortices of the cat and rat. The data given in their paper applies to Area 3 (Krieg) of the somatosensory cortex of the rat. The bundle size ranges from 4-6 dendrites of the layer V medium and large pyramidal cells, up to about 14 (Fig. 10). SzentagothaissJss, including the layer III pyramidal cells in the bundling, states that there are approximately 20-30 neurons involved in each bundle. The bundling disappears in layer 11 through dendritic arborization and bundle merging. Peters and Walsh find that the cell bodies are grouped below the dendritic bundle. The distance between the bundles is typically of the order of 50 pm, while between the larger bundles it is approximately 150 pm. The authors point out that since the basilar dendrites and apical tufts spread horizontally for approximately 100 pm, there must be some overlap with those in the neighboring bundles. It is also noted that columns in the somatosensory cortex of the cat have a diameter of the order of 500 pm, i.e. bundles are not columns (see later discussion on columns). Peters and Walsh think it likely that the dendrites in a bundle (along with the corresponding neurons) share a common afferent input, judging from electron microscopy studies
257
Fig. 9, Drawing near crown of precruciate gyrus, pr, showing the types of pyramidal cells in the six cortical layers. In layers 2, 3, and 5, the pyramids’ basilar dendrites form thick horizontal neuropil fields at a, b, and c. The giant pyramids of Betz in layer 5 generate very long basilar dendrites which form bundles, d. Apical dendrites also may form bundles, e. x 240. From a single section of adult cat cortex. Golgi modification. (From ref. 62.)
show an accumulation of small unmyelinated axons and terminals encompassing a bundle, and synapsing with the dendrites in the bundle. From these observations, Peters and Walsh suggest that perhaps bundles are organizational compowhich
nents of columns. Fleischhauer et a1.21-24,47 and Detzer I4915 studied the somatosensory cortex of the rabbit and cat. They find approximately 15 dendrites (about 6 from layer V pyramidal cells) per bundle in the rabbit somatosensory cortex. Most of the dendrites in the region appear to enter into bundles. The typical bundle diameter (rabbit) is 20-35 ,um. Again, the distance between bundles is found to be of the order of 50 ;l.rn (rabbit). As in the studies of the Scheibels above, it is mentioned that Lhe bundle gains and loses dendrites along its length. The dendrites lie closely together, with some ‘separated by extracellular space only.’ With regard to this, MPrllgard and Mraller50
258
IV,
VA
Fig. 10. Reconstruction of a cluster (bundle) from a series of tangential 1 /cm sections, segmented to show the relationships of the dendrites as they approach the cortical surface. (From ref. 55.j
of dendrodendritic gap junctions between the dendrites in a bundle. Fleischhauer et al.21-24 and Detzer 14115have compared the somatosensory and visual cortices of the rabbit and cat. They find, typically, 2-3 dendrites (from layer V
suggest the possibility
259
8
b
Fig. 1I. Diagram of the dendritic bundling patterns in the visual cortex (a) and the somatosensory cortex (b) of the cat. (From ref. 21.)
pyramidal cells) per bundle in the cat, and about 5 in the rabbit visual cortex (compared to 6 dendrites from layer V cells observed in the typical bundle of the rabbit’s somatosensory cortex). It is found that bundling follows different patterns in different regions (e.g. see Fig. 1 I). Fleischhauer et al.24 propose that dendritic bundling serves to synchronize firing among the neurons involved. Petsche et al. 57 also suggest synchronization as a function of bundles since layer V neurons are connected through bundling to the generator layers 11 and III. Other researchers have also found bundling among the apical dendrites of pyramidal cells in the cerebral cortex. Stahl and Broderson86JJ7 have identified (histochemicaily) what they believe to be bundIes of apical dendrites from pyramidal cells in the somatosensory cortex of the rat which run from Iayer V to layer Ii, arborizing in layers II, III and 1V. Bundling has been observed in the motor cortex of the cat”JJ-7 and the rhesus monkeysz. In the cat there are from 2 to 7 neurons involved in the formation of a bundle. The neurons tend to lie beneath each other; when a Betz cell is present, it is often in the center of the neuron group. The distance between bundles ranges from 50 to 100 pm. Here again, dendrites tend to wind around each other, and the dendrites are frequently in contact. As elsewhere, bundles gain and lose dendrites along their length. Between the dendrites, running perpendicularly, are small axons which form synapses with the bundle dendrites. Babmindra et al .2,3 also identify dendrodendritic contacts. In the monkey motor cortex, Sloper82 associates degenerating thalamocortical terminals with bundles in layers IV and III. In a quantitative study, the terminals are shown to be found more frequently where apical dendrites are most numerous. There is an apparent correlation between terminal location and the number of apical dendrites at that location. He also cites Garey and Powell26 who have found
260 that, in the visual cortex, degenerating
thalamocortical
terminals
seem to be grouped
at about 100 !drn intervals, possibly related to the intervals between bundles found in that region (see results of Von Bonin and Mehler, Winkelmann et al. and Feldman and Peters below). The groups of dendrites Von Bonin
and
Mehler”5
macaque
cortex
bundles. (bundles)
Von Bonin and of approximately
found by Fifkova”O in the visual cortex of the rat and by in Brodman’s
have been reexamined
areas 4, 17, 7 and 40 of the human by Peters and Walsh55 and interpreted
Mehler cite a distance 80 pm.
between
the groups
and as
of dendrites
Winkelmann et al.9’ have found bundles in the visual cortex of the rat. The number of dendrites per bundle averages about 5 in lower layer Vb to about 8 in upper layer Va. The average bundle diameter is given as 26 ,um, with an average distance between bundle centers of 76 /lrn (53 /Am between bundle peripheries). Feldman and Peters” have found bundles of apical dendrites pyramidal cells in :
of’ layer
V
(a) Krieg areas 2, 3 (somatosensory cortex), 4, I7 (primary visual cortex), 41 (primary auditory cortex), the cortex of the frontal pole and ‘barrel field’ of the rat: (b) postcruciate gyrus, primary visual cortex, primary auditory cortex. somatosensory cortex, and the cortex of the frontal pole of the cat; (c) area I of somatosensory cortex, auditory cortex, primary visual cortex of the frontal pole of the macaque and of the human; and (d) neocortex of the opossum.
cortex,
and
They find 6-8 dendrites per bundle in the rat’s somatosensory cortex, with a distance between the bundles in the rat’s visual cortex of 30-40 pm. They see no spatial relationship between the barrels and the bundles in the rat’s parietal cortex. The separation between bundles in the cat’s auditory cortex is estimated as 50-70 pm. Feldman and Peters, like Fleischhauer, note that in the cat bundling patterns differ in different regions, e.g. the postcruciate gyrus has more dendrites per bundle than the auditory or visual cortices, but that the auditory and visual cortices are similar. Whereas Feldman and Peters observe no relation between the barrels and bundles in rat parietal cortex, Whites6 and Detzerta, who have studied bundles of apical dendrites in the barrel field of the mouse, both find bundles of dendrites located predominantly in the sides of, and in areas between, barrels. Fleischhauer and DetzeF also observed bundling in the barrel field, parietal cortex, and striate region of the mouse. Schierhorn’s
studied the development
of bundling
of apical dendrites
of iayer V
pyramidal cells in the sensorimotor cortex of the albino rat. He finds that by 4 days after birth a loose bundle-like order is observed. By 24days after birth, dendritic bundles are clearly visible. At 36 days there are about 3 dendrites per bundle; at 90 days there are up to 6 dendrites in a bundle. The dendrites appear entangled, possibly allowing more contact
between them. processes in the Bundling has been found by Ms11gard49 among the neuroblast visual cortex of the (3-4-month-old) fetal human brain. Msllgard identified dendrodendritic gap junctions amongst the processes as well. It is suggested that bundles
261
Fig. 12. Betz cell (b) with a primarily cylindrical dendritic domain. The group of pyramidal cellsat aare to be centered on the + in the dendrite domain in b. Many of the apical dendrites of the group of cells appear to form bundles (c) with the descending dendrites of the Betz cell. Section cut perpendicular to surface. (From ref. 75.)
could be electrotonically coupled (by dendrodendritic gap junctions) units which came from neuroblasts lined up in the same vertical row. Peters and Feldman56 find no evidence of bundling of the apical processes of immature neuroblasts in the cortical plate of the 19-21-day-old fetal rat cortex. However, the beginnings of bundling appear among the dendrites of more mature nerve cells. Dasll observed bundling in the dorsal developing neocortex of the 8-day-old rat embryo transplanted into the cerebellum of a IO-day-old rat. If the pyramidal cells were grouped together, their dendrites grouped into bundles, with entire dendrite lengths in one bundle. Das suggests that bundling may depend on the grouping of pyramidal cells and other developmental events. 2.4.2. Basilar dendritic bundling The basilar dendrites of the giant pyramidal cells of Betz and the large solitary cells of Meynert in the primary motor and visual cortices have been found to form bundles in the monkey, cat, mouse, and rat62 (Fig. 8). In human motor cortex64975 (Figs. 12 and 13) the basilar dendrites of Betz cells form bundles with the apical and basilar dendrites of other pyramidal cells. The results in ref. 62 are given for Betz cells but also apply to Meynert cells. The number of dendrites (of Betzctlls) per bundle
Fig. 13. Betz cell (b) with large dendrite angling downward into pyramidal cell groups. Dendrite shaft and branches form bundles with the pyramidal cell basilar dendrites. Section cut perpendicular to surface. (From ref. 75.)
varies, ranging up to 6-10 in the cat, 3-8 in humans. About 50”/, of the bundles in humans have one dendrite from a Betz cell (identified as the dendrite profiles with diameter of more than 8 ,um; some of the smaller profiles may also be from Betz cells). In 7 out of 24 bundles, 1 or 2 smaller dendrites partially encircle a large dendrite, possibly increasing the chance for contact. In general, the dendrites are separated by lo-20
nm in the human,
frequently
with nothing
between
the membranes.
As in
bundling in other regions, dendrites may join or leave the bundle along its course. The bundles are several thousand /Am in length, with a diameter (in humans) of 12-40 pm. As the basilar dendrites of Betz cells spread to a 2 mm diameter circular field, the authors
point outs” that 4 giant cells can lie along the basilar dendrite
of one cell
(the distance between cells averages 240$45 pm). Bundling between thecells’dendrites could possibly bind a column (see discussion on columns below), roughly defined by the dendritic field of one Betr cell, to other columns. It is also suggested62 that bundles might serve as the location of programming for ‘sequencing and modulating phasic discharge patterns of Betz cell complexes.’ From the human study, it is proposed that, with age, the decreasing number of horizontal dendrites may lead to ‘progressive diminution of central program storage areas.’ 2.5. Comparisons Few comparisons
can be made of these neuroanatomical
results as studies have
263 seldom
been done in the same brain
lamina
IX of the cat spinal cord we can compare
and (2) Matthews
regions
with quantified
results.
Of the few, in
the results of (1) the ScheibelsGT,68
et aL4s:
5-20 20-60 jrm 1OO-several hundred [rm 0.2-0.5 jrrn and occasional direct membrane apposition (electron microscopy)
3-25
Number of dendrites per bundle: Bundle diameter: Length of dendrite while in bundle:
I O-70 I’m 400-600 /trncR (500-700 (lrnGT) 2 I’m or less (light microscopy)
Distance between dendrites in bundle:
In addition to these results, which are fairly consistent, both researchers observe that a bundle gains and loses dendrites along its length. In lamina IX of rat spinal cord, we can compare the number of dendrites in a bundle found by Anderson
et a1.l and by Kerns and Peters41 (about
1200-1600 vs over
1400), and we can compare values for bundle diameter (largest, 910 pm vs 2.50 pm). In rat somatosensory cortex, we have the results of (1) Peters and Walsh55, (2) Feldman and PetersIT, (3) Schierhorn ‘i6, and (4) Stahl and Brodersonss,s7:
Number of dendrites per bundle: Dendrite diameter:
(1)
(2)
(3)
(4)
4--6 up to 14 3-8 jlrn (layer IV)
6-8
-6
-
-
3-5 ,um (min.)
In rat visual cortex the distance between bundles is 30-40 pm as measured Feldman and Peters17 and 76 pm, according to Winkelman et a1.g7. 3. PHYSIOLOGICAL
Although
MODELS
dendritic
bundling
has been found
experiments throughout the brain, determine the undoubtedly important we presented
by
several possible
function. In this Section, physiological models.
in numerous
neuroanatomical
there have been no physiological studies to functions of this bundling! In the Introduction,
physiological
we discuss,
roles that bundles
in a little
more
detail,
might
play in brain
several
aspects
of
An important first point is to clearly distinguish between bundles and columns. Bundles are in genera1 smaller than columns; Peters and Walsh55 suggest that a group of bundles may form a column. For completeness, we briefly discuss some aspects of columns, which are not observed anatomically, but are seen through their physiological function, in contradistinction to the situation for bundles. For more detail on columns, see the recent review by Mountcastless. 3. I. Columns The cerebra1 cortex
appears
to be organized
in columns
of lOs-lo4
intercon-
264
\
Fig. 14. Idealized model of striate cortex with two orientation hypercolumns (each 180”) and two ocular dominance hypercolumns. Columnar walls are actually not flat and the intersections not strictly perpendicular. R, right eye. L, left eye. (From ref. 36.)
netted cells running through the cortical layers, perpendicular to the pial surface. The column is defined by its thalamocortical afferents and by its patterns of functional response, i.e. all cells in a column respond to the same sensory modality and have roughly the same receptive field. In addition to being a physiologically vertically organized unit, a column is also somewhat anatomically vertically arranged, with primarily vertical connections between the neurons. An active column inhibits the firing of neurons in the neighboring columns, making electrical activity in the cortex even more vertically oriented. Note that the columns are not visible by ordinary histological staining methods, but are identified as physiological units, originally by recording the electrical firing response of individual neurons to sensory input, and more recently by labeling techniques: by transneuronal autoradiography and by the clever [14C]2deoxyglucose method of Sokoloff 40~33. Mountcastle, the first to identify columns, found that the somatosensory cortex has columns with diameters of roughly 500 ,urnsl. The best studied area is the primary visual cortex, where the beautiful experiments of Hubel and Wiesels*-36 have demonstrated that there are two independent partitions as shown in the totally idealized model of Fig. 14. Pyramidal cells in each column yield the maximum number of spikes when the animal is stimulated by short line segments
26.5 (in a given region of the visual field) which have a given orientation and are excited by the left (L) or right eye (R). The dimension associated with an orientation column is ,50 pm whereas the dimension of an ocular dominance column is - 400 pm. Hubel and Wiesel also define hypercolumns which comprise a complete 180” discrimination in orientation (-600 pm) and L-R ocular dominance (-800 pm). A recent studysG has clearly established the grid but shows that the boundaries of the columns are not sharp and regular as in the idealized model of Fig. 14. Goldman and Nauta27 have found columns located throughout the mammalian cerebral cortex, so that we may consider columns as a general organizational feature of the cortex. Mountcastle has recently presented a very interesting organizational model of the brain52. He regards the (macro~olumn) column, of some 500 pm in diameter, as the basic processing unit (with interactions among the macrocolumns~. Each column consists of basic modular subunits of neurons, or minicolumns, roughly 30 pm in diameter, put together in such a manner that the (macrocolumn) column can perform its appropriate processing or memory storage tasks. Although Mountcastle does not make this identification, we propose that vertical dendrite bundles may constitute the minicolumns or basic subunits of the columns he discusses. Shaw and RoneyslsO have presented a specific, testable mathematical realization of the combined organizational ideas of Mountcastle and the learning hypothesis of Hebb30. Incorporating the known statistical nature of chemical transmission at the synapseag, Little and Shaw42,43?79$*1 d eveloped a model of memory based on the Hebb pre-post-synaptic modi~cation hypothesis. Analytic solutions to this mathematical model were obtained showing very interesting behavior. However, in order to obtain a complete, fully interpretable theory, Shaw and Roney were forced to introduce a Mountcastle-like organizational structure! The result was a network of 103-10” highly interconnected neurons, corresponding to a cortical (macrocolumn or hypercolumn) column, which was divided into assemblies consisting of roughly 20 neurons. It was shown that the average output of the neurons in an assembly to a single stimulus presentation to the column was equivalent to the post-stimulus histogram (PSH) of an individual neuron in the assembly, the PSH being obtained by averaging the output of the neuron over - 20 presentations of the stimulus to the column. In response to a ‘meaningful’ stimulus, the network (column) will be excited into one of many different sequences of {averaged) firing patterns in which the activity flows from assembly to assembly. persisting for some fraction of a second. The columns interact directly and/or through thalamocortical pathways. A number of interesting, testable predictions followed. A key input into this theory was the assumption that the neurons in this (subunit) assembly were closely coupled electrically. We suggest that the subunits (minicolumns), or assemblies of this model, are the anatomically identified bundles. Support for this equivalence comes from the likely common afferent input to a bundle suggested by Peters and Walshss, which is consistent with the possibility of averaging taking place within the bundle (which defines the theoretical assembly). The possibility suggested by several experimenters of dendrodendritic gap junctions (see Table 111, ‘Features’) also supports the averaging hypothesis, with the dendrodendritic junctions acting as the coupling mechanism. Schmitt et al .‘i8 suggest bundles as ‘ideally suited for
266
d
B Fig. IS. Summary figureindicating the possible location and substrate for macromolecular coding of stored output patterns. A: model of the extended membrane modified slightly from Lehninger (Pwc. j7af. Acnd. Sci. (Wash.), 60 (1968) 1055-I 101). The neuronal plasma membrane is the dynamic interface between the extraneuronal space, a, and the cellular cytoplasm, b. Its inner zone. c, a liquidprotein complex bears a more diffuse, covalently linked outer zone, d, composed of ohgosaccharide chains, e, capped by negatively charged sialic acid moities, f. B: cross-section through a typical dendritic bundle in cerebral cortex, based on tracings from electron photographs (approximately 20,000 :-). The arrow points to one interface between closely apposed dendrite membranes. C: an hypothesized enlargement of the area noted in B. In the interval between the membranes of two dendrites crosssections, a and b, oligosaccharide-sialic acid side chains extend toward each other, immersed in the hyaluronate rich extraneural space (shaded area). (From ref. 71.)
the interaction
of dendrites
through
extracellular
fields’, which is another
possible
averaging mechanism. Other support for bundles being assemblies is that the typical size of a bundle is of the same order as the size hypothesized for the theoretical assembly. Difficult physiological experiments are necessary to test these assumptions and predictions. For more details see ref. 79. Macromolecular coding of stored output patterns has been suggested by Scheibel and Scheibel~‘~‘~ as a possible mechanism for inscribing central programs within dendrite bundles. It is hypothesized that the intrafascicular spaces within the bundle, and especially those between closely opposed dendrite shafts, provide a sheltered micromilieu affording opportunities for physical interdigitation and chemical interaction among the macromolecular projections (Fig. 15). Cation-mediated linkages established between adjacent polyamines making up the membrane outer surface may operate under increasingly predictable sets of input-output restrictions, the latter possibly repre tented by characteristic patterns of electrotonic coupling potentials. The resultant stabilization of these links associated with large changes in
267 hydration and an increase in polysaccharide concentration could lead to formalization of steric configurations. These stabilized steric macromolecular patterns may contain the coded program determining output characteristics of the dendrite bundle’s corresponding neurons. The actual nature of the coding scheme has yet to be determined. All bundling probably does not serve the same function. In the case of Betz ceils, bundling extends over more than a column’s diameter, In this case, perhaps the bundles perform the task of providing the inhibition between neighboring columns as discussed above, In the spinal cord of the rat, bundles are found to be formed of 1200-1600 dendrites. Great reliability may be the principal function of bundles here. Predominantly, however, there are the smaller bundles of the order of 20 dendrites, with diameters of the order of 50 jcm. In order to determine the functions of bundling, it is necessary to determine whether there is coupling, electrotonic or otherwise, among the dendrites in a bundle. If there is coupling, the bundling could serve as an averaging mechanism, uniting the neurons involved into an assembly, possibly acting as Mountcastle’s column subunit. Firing correlations could be determined between neurons having dendrites in the same bundle and in different bundles. The experiment will require the use of two or more closely spaced extracellular microelectrodes, as in the work of Verzeanosa,93, so as to determine the relevant correlations between neurons within the same bundle, within neighboring bundles, and within bundles in different columns (networks~. In addition the dendrite systems of these neurons would need to be visually identified and their presence in the same (or different) bundle(s) verified. Only the most rigorous speci~cation of dendrite membrane continuity would provide a reasonable basis for the assumption that correlation of firing patterns between neurons might be due to dendritic coupling phenomena. This experiment would also indicate whether firing activity moves from one bundle to another, as discussed above. Another possible experiment would be to determine whether there is a correlation between brain area and the number of dendrites per bundle. Regions with a large number of bundled dendrites (as in rat spinal cord) might be expected to be regions where high reliability is needed. Perhaps a region with a smaller number of neurons is one where greater flexibility and processing or storage capacity is needed. Other interesting experiments would be to further determine the pattern of bundle development in the neocortex (see discussion of bundle development in the neocortex and its possible role in Sudden Infant Death Syndrome above). The development of bundling after birth may possibly reveal significant correlations to learning and behavior. These and other physiological experiments, although difficult, are necessary in order to clarify the role of bundles in brain function. 4. SUMMARY
Dendritic bundles have been found throughout the mammalian brain. Unquestionably, these bundles must serve one or more important, fundamental roles in the brain’s fulictioning. However, no physiological experiments to determine their
268 function
have been performed
the numerous
anatomical
logical possibilities
on these well-established
reports
of bundling.
for the functional
anatomical
In addition,
significance
units. We survq
we discuss several physio-
of bundles.
ACKNOWLEDGEMENTS
Some of the original ported
by USPHS
K.J.R.
is supported
Grants
studies on dendrite NINDS-01063,
by an IBM predoctoral
bundle
structure
NINDS-10567,
by A.B.S. were sup-
HD-00972
and NB-01063.
award.
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96 White, E. L., Ultrastructure and synaptic contacts in barrels of mouse SI cortex, Brain Researr,h, 105 (1976) 229-251. 97 Winkelmann, E., Brauer, K. and Berger, U., On the columnar organization of pyramidal cells in visual cortex of the albino rat, Z. ~?j~~u~~.-a~at. Forsch., 89 (1975) 239-256. 98 Wuerker, R. B. and Palay, S. L., Neurofilaments and microtubules in anterior horn cells of the rat, Tissue and Ceil, 1 (1969) 387402. Reference search ended October, 1978. Our apologies to those authors we may have overlooked.
f3rain Research Reviews, 1 (1979) 225-271
DENDRITIC BUNDLES: SURVEY OF ANATOMICAL PHYSIOLOGICAL THEORIES
EXPERIMENTS
KATHLEEN
L. SHAW
J. RONEY, ARNOLD
3. SCHEIBEL*
and GORDON
AND
Department of Physics, University of CalifortGa, Irvine, Calif. 92717 and (A.B.S.) Departments of Anatomy and Psychiatry and the Brain Research Institute, U.C.L.A. Center for the Health Sciences, Los Angeles, Catif 90024 (U.S.A.) (Accepted May 11th, 1979)
Kq
wor&:
dendrites
-
mammalian
brain
-
dendritic
bundles
-
Golgi
studies
LIST OF CONTENTS
.
I. Introduction
. . . . . . . .
2. Anatomical experiments . , 2.1. Spinal cord . . . . 2.2. Brain stem . . . . 2.3. Other areas . . . . 2.4. Cerebral cortex . 2.4.1. Apical dendritic 2.4.2. Basilar dendritic 2.5. Comparisons . .
. . . . . .
.
. . . , . . .
Acknowledgements References
.
. . , . . .
.
. . . , .
228
.
I
. .
. .
. . . .
.
. . . . I
, , .
. . . . . . , . . . . . . . . . . .
225
228
. . .
.
3. Physiological models . . . . . . . . . . . . 3.1. Columns . . . . . . , . . . . , . 4. Summary
.
.
. . . . . . . . .
.
. .
. . . .
bundling bundling
. . . . . . . . . . .
f .
249 252 253 256 261 262
.
263 263
.
.
261
. . . . , . . . . . , ,
.
268
. . . . . , . .
. . . . . . .
.
_ . .
268
1. INTRODUCTION Dendritic bundles (or clusters), which have been found throughout the mammalian brain, are unquestionably important, fundamental units involved in the brain’s functioning. However, no physiological experiments to determine their role have been performed on these well-established anatomical units! The purpose of this paper is to survey the numerous anatomical reports of bundling. We summarize the results in
* To whom correspondence
should be addressed.
226
Tables I through IV which we hope will be useful for those planning future anatomical and/or physiological experiments as well as for model builders. For illustrative purposes, we briefly discuss several physiological possibilities for the functional significance of bundles. Dendritic bundling does not necessarily have a single function but could serve in a variety of ways in different regions of the brain, e.g. as an electrophysiological unit involved in processing, as a mechanism of synchronization among neurons, as a metabolic transfer mechanism involved in neuronal maintenance, as a developmental unit important to brain growth, and 50 on. We briefly discuss a theory in which the bundles have the first-mentioned function, i.e. they act together as processing units. Very brief allusions to dendrite bundles were made by Cajal at the beginning of this century in the visual cortex’” (see also Fig. 388 of ref. IO) and by Laruelle (as noted by Barron”) in the spinal cord. These observations were forgotten, and it was not until 1970 that dendritic bundling was studied in detail. Recently, modified Golgi stains and a number of other techniques have been employed (see Table IV) which reveal a larger number of the neurons present in a region and thus enable the observation of the striking features of dendritic bundling. Dendritic bundles are groupings of dendrites which course along very closely together (typically, from 1 pm apart to direct membrane apposition) in the brain. They are a relatively general feature of the mammalian brain, having been found by many groups in the spinal cord, brain stem, cerebral cortex, nucleus reticularis thalami. habenular nucleus, and olfactory bulb. Most bundle complexes include IO-20 dendrites (with wide variation), with a bundle diameter of roughly 50 /tm and a distance between the bundles of the order of 50 pm. Thus, bundles ate not columns (see later discussion on columns) but are much smaller units. There have been many anatomical studies of bundling but, to our knowledge, no electrophysiological investigation. The importance of examining bundles electrophysiologically (and otherwise) is seen in their possible roles which are important to brain function, as follows.
(A)
Maintenance of the circulation of neuronal firing activity It has been estimated that upon the presentation of a ‘meaningful’ stimulus, a
network of neurons maintains related reverberatory firing activity for approximately I secso. Lorente de No*4 long ago realized that activity in short, simple circuits of neurons could not persist for such a long period (compared to the several msec associated with the recovery time after neuronal firing). Hebb recognized the difficulties in functionally linking in a simple circuit the large number of neurons necessary to account for the reverberatory time. Accordingly, he suggested that the firing activity of a network moves from one unit to another, for perhaps 1 sec. Bundles of dendrites could conceivably act as Hebb’s functional units. (Bj
Stability
against local brain damage
The individual neuron in a network cannot be the fundamental
element in
227 storing
information
local damage as is provided
as many neurons
die at random
and are not replaced.
should not destroy the stored information, by an assembly
(or bundle)
(C) Statistical reliabilit?’ It is known9,r6J*~sg,g0
that, although
to one stimulus
to an animal
presentation
some ‘back-up’
As limited system such
is necessary.
the spike trainresponse is not reproducible,
a single neuron to many presentations (the post-stimulus cible. However, since behavioral correlates are repeatable
of a singleneuron
the average response
of
histogram, PSH) is reprodufor a single presentation of a
stimulus, we expect that the firing response of some appropriate set of neurons is also repeatable. It has been suggested ss,79 that the spike train response to a single stimulus presentation averaged across many neurons in an assembly is the same as the PSH (determined by averaging the responses from many (~20) presentations of the same stimulus) of a single neuron in that assembly. This hypothesis defines the assembly as a localized group of neurons assemblies.
obeying this averaging.
Perhaps bundles are these theoretical
(D) Insurance of a reasonable memory storage capacity A theory developed by Shaw and Little 4a,4s,7s,st involving a network of neurons having Hebb-type modifiable synapses so showed the storage capacity to be related to the number of synapses. This result implied that the network can be excited into many different time sequences of firing patterns of assemblies of neurons (defined by the relationship in (C)), possibly bundles.
(E) Synchronization function Bundles could perhaps rather than having a processing
(F) Non-electrical
provide
a means
of synchronization
among
neurons,
function.
functions
Other possible roles of bundles in the nervous metabolic functions.
system include developmental
and
Bundling may have any of these functions or serve several purposes in different the brain. One very interesting possible function of bundling in the reticular suggested by Scheibel et al.63 and now with some experimental support, is role of programming location for ‘rhythmic repetitive output’ such as respithe rest-activity cycle. In the widest sense, dendritic bundling could act as a
regions of formation, that of the ration and
possible basis for coded memory output patterns (see refs. 71 and 73). In the study of the reticular formation of the cat, they find a progressive loss of spines and formation of dendritic bundles in the normal course of development in the kitten. Of enormous interest are the preliminary results of Quattrochi et al.s8 who have found that in Sudden Death Syndrome infants, bundling of the dendrites has not taken place and there is no apparent loss of spines. In control studies of infants of similar age dying of
228 ‘other causes’, however, the loss of spines and formation of bundles has occurred just as in the young cats. We feel that it is of the utmost importance that appropriate physiological experiments be done in order to determine the functional role or roles that these wellestablished, well-studied anatomical bundles of dendrites play in brain function. 2. ANATOMICAL
EXPERIMENTS
In this section we summarize the results of neuroanatomical work by many groups on dendrite bundles in the spinal cord, brain stem, nucleus reticularis thalami, olfactory bulb, habenular nucleus, and cerebral cortex of various mammals. We present the authors’ work, including their suggestions as to the possible functions of bundling. The information is presented in more detail in Tables I through 1V. The various staining techniques used are included in Table IV, and it must be understood that these techniques differ to some extent in the degree of their quantitative rigor. 2. I.
Spinal
cord
The lumbosacral ventral horn (lamina IX) of the spinal cord has been shown to be a site of rostrocaudal dendritic bundling in the monkeyes, cat12J5~~8Jji~68,pig”“. and ratl~~~*~~.The number of dendrites found per bundle varies, generally in the range 5-20, although in the rat the number is found to be of the order of 1200-1600 dendrites1s4’. A bundle gains and loses dendrites along its length. It is estimated68 that 80 % of the dendrites in the region form into bundles. Individual dendrites of a neuron may enter into different bundles, and dendrites from neurons in separate motor cell columns can be in the same bundle6*. The characteristic size of a bundle in this region of the spinal cord appears to be several millimeters in length68, with a diameter of the order of 50 pm, again excepting the large rat bundles found by Anderson et al.1 (maximum -1000 pm diameter) and Kerns and Peter?’ (250 pm in diameter). The distance between the dendrites in a bundle is generally reported as 2 ,um or less with some separations unresolvable by light microscopy68. Matthew et a1.48,using electron microscopy, observe some separations of 0.2-0.5 pm (Fig. I) and occasional direct apposition of membranes, including both unspecialized contact and those with electron opaque material present. Anderson, also using electron microscopy, found desmosomal dendrodendritic contacts amongst the bundled dendrites. An interesting occurrence in this regions4 is that spinal catecholamine nerve terminals from locus coeruleus, after being lesioned with 6-hydroxydopamine intracisternally, regenerate ‘as if growth was guided by the longitudinally running dendritic bundles of the motorneurons’. The ScheibeW.88 have suggested that the role of dendritic bundles in lamina IX of the lumbosacral spinal cord is to serve as a source for the program governing reciproval activity of muscle pairs in the hind limb in walking, stepping, and SO on. In support of this hypothesis is the developmental pattern of the bundles in this regions7
229 (Fig, 2). The bundles are not present at birth but develop (in the kitten) near the end of the second week, corresponding to the time when the kitten starts using its hind limbs for weight bearing and walking. By the fourth or fifth month the bundles appear fully developed and the complete repertoire of hind limb behavior has been achieved. Electromyograms
recorded
agonist-antagonist
at parallel
times show that reciprocal
activity
between
an
muscle pair is absent at birth, begins to appear at 12-14 days and is
fully developed
by the fourth
or fifth month.
Anderson
et a1.l doubt
this role of
bundling, stating that the sixth lumbar segment (where bundling was found in the rat) is only minimally involved in hind limb control. Matthews et al.48 have suggested synchronization of neuronal firing as the function of bundles in this region, based on the closeness of the dendrites involved in a bundle. Weak electrical facilitation is known to exist between cat spinal cord neurons 53; Matthews believes this might be made possible
by the contacts
al.s4,s5, however,
occurring
think there is not enough
between
dendrites
direct apposition
in a bundle. of dendritic
Sotelo
et
membranes
to consider ephaptic interaction possible. Dendritic bundles have also been found in the ventral horn of the cervical and ventroenlargement of the spinal cord of the cat69, especially in the ventromedial lateral areas. In this region the bundles are present at birth; their length increases with age (at 3-4 days, 50-100 pm; at 12-l 4 days, 150-200 pm). The region is responsible for forelimb muscle control, particularly in the proximal portions of the limb. It is hypothesized that the dendritic bundles are the storage sites for programming the reciprocal activity of muscle pairs in the forelimb for, for example, the treading reflex in the suckling kitten. The Scheibels72 have found dendritic bundles running perpendicularly to the rostrocaudal axis in the ventral commissure of both cervical and lumbosacral segments of the spinal cord of the cat (Fig. 3). Here, dendrites from both motoneurons and interneurons appear to be involved in the bundling, with up to lo-15 dendrites per bundle. A bundle may include dendrites from both medial and lateral motoneuron pools representing cells supplying muscles with both agonist and antagonist functions. Contralateral
motoneurons
lose dendrites
along its length of 100-500 pm. Also, individual
may extend into different with light microscopy
may be involved. bundles.
among
Again,
the bundle
is seen to gain and
dendrites
And as in other cases, no separation
many
of the dendrites.
These bundles
of a single cell is resolvable are present
at
birth. As the commissure in the cervical (lumbosacral) segment is responsible for coordination of arm (leg) movement, it is suggested 72 that the bundles could serve as program sites for ‘reflexive response sequences involving pairs of extremities, such as stepping and walking.’ Bundles have been found by several investigators in the ventral horn of the cervical12, thoracic12,2s and sacralla portions of the spinal cord of the cat as well as in the lateral motor nucleus of the cervical spinal cord of the fetal mousega. Bundles are possibly present (although the authors did not so state) in the intermediolateral nucleus of the thoracic spinal cord of the cat60 and in the anterior horn of the cervical spinal cord of the ratgs.
.
.fkatures o/’ dendrite
:
Motoneurons (mainly) f interneurons Motoneurons
Motoneurons
“* Dendrite3
Bundle
Bundle
Several mm
length
Largest 910 jtm
250 jrm
1200. -1600
Over 1400
2.4mm
jrm --
20.6Ojlm
IO-70 jtm (cat)
diamerer
55-85
-807:
-_
enter. bundle
up to 12
5-20(tertiary and secondary dendrites mainly. occasionally primary) 4ormoreper area 25 pm *. 25 jirn
Motoneurons
per bundle
per bundle
3-25 (cat)
NO. neurons
No. dendrites
Motoneurons
Type of neurotr
bundles
5 Lamina 1X of L7, St, SZ, Ss segments of spinal cord of pig4’ Motoneurons 6 (Ventrolateral) ventral horn of lumbar (Ltl) spinal fusiform cord of rat (2 groups of bundles : (I ) lateral and (2) medial, running perpendicularly)r Motoncurons 7 (Ventrolateral) ventral horn of lumbar (La) spinal cord of rat (also bundles in ventromedial and dorsolateral regions of ventral horn, but bundlessmaller)J’
3. Ventral horn (lamina VII, VIIIandIX)ofC2-Cs,Tr, Ja, TIN, L1-L7, SJ, s2 segments of spinal cord of cat (lamina 1X only in enlarpments)12 3 Lumbosacral spinal cord (motor nudei) of cat45
1. Ventral horn of lumbosacral spinal cord of cat and monkeys7.6s 2. Lanka IX of LR,L7.S segments of spinal cord of Lx@
Spinol cord
Area
Quonrirative
TABLE I
Dendrite
5 7.5
jlm
diameter
Mean: 2 jcm (0.2-4jdm) 88 y/, have
Ave. 1.7 jim
7- 14 jrm
Variow
.--
diameter
of dendrite
.-
Ave. : 63 pm
IOO-several hundred jlrn
Ave. : 400-600j~mtin WO-700 jtms7
while in bundle
Length
!
I
I i
I
i
I I
i !
/
1
I I
of
dendrites)
(apical
Layer V pyramidal
(apical
monkey”” Area 17, visual cortcy ~,f
rat20
13
areas 4, 17, 7
25. Visual
of rat”’
cortexg5
cortex
macaque
and 40 of human and
24. Brodman’s
of rhesus
Motor
V medium
dendrites)
dendrites)
dendrites)
Q 5 (iowcr laqcl-
dendrites)
Vb) - 7.5 (uppe1laver Va)
--
V cells, catj
2-3 (from layer
rabbit)
layer V cells,
(cat) - 5 (from
Layer Vpyramidal
dendrites)
below)
(apical
(apical
Pyramidal
(apical
Pyramidal
(apical
and large pyramidal
Layer
(presumably)
V pyramical
Layer
Layer V pyramidal (apical dendrites)
to 50
areas; (gurus genualis)
2 (striate see
rabbit)
- 15 (total,
dcndritez)
(apical
22
cortex
layer
rabbit)
h 6(in IV,
layer IV cells)
(
layer V
seeing dendrite bundles) Motor cortex of cat2*“*” i
to assume’
Large
pyramidal
21.
‘reasonable
20. Somatosensory cortex of rat*6,*7 (not definite, but
cat alone?l
19. Visual cortex of rabbit and ofcat”, rabbit alone’“*d”,
cat,
alone*+I”~37
rabbit
alonezl
cortex and catZs,2”.‘J,
rabbit
18. Somatosensory
dendrires per bundle
3-4 2-3to5-7
‘Majorit),’ (rabbit)
IX-35
,I,“,
layer Ill)
2 4ttm(in
layer V)
4 b/cm(in
min.
3 5j/rn
-..
.--.
ratT6
Pyramidaf (apical dendrites) Layer V pyramidal (apical dendrites) Layer V pyramidal ( +- layer 1V cetk. in area parietalis) (apical dendrites) Layer Vpyramidal (apicoi dendrites) Layer V pyramidal (apical dendrites)
Layer V pyramidal @pica!. dendrites)
Layer V pyramidal (apical dendrites)
Layer V pyramidal (apical dendrites)
Layer V pyramidal (apical dendrites)
35. Visual cortex of human fe- Neurohlasls tal brain (34-month-old)1~ 36. Corlical plateofIate(l%lMature ncurobiasts day) fetal rat cortexs~ Pyramidal 37. Dorsal developing neo(apical dendrites) cortex of&day-ald rat embryo, transpl~l~tcd~nto
albino
33. Barrel field, parietal cortex, striate region in mouse2s 34. Sensorimotorcnrtex of
32. Barrel field and ruea parictalis ot mouset3
3). Barrel field of mousers
28. Cortex of frontal pole, area t ofSS cortex, auditory cortex, primary visual cortex of macaquer’ 29. Cortex of frontal pole, SS and auditory cortices, primary visual cortex of humanr7 30. Opossum neocortexr7
26. Krieg areas 2, 3 (SS cortex) 4,17 (visual),41 (auditory), cortexoffrontal polc,and ‘barrel field’ of ratA7 27. Postcruciate gyrus, primary visual cortex, primary auditorycortex,SScortex, cortex offrontai pole ofcat”
-__
-
-
_l.l
--.
-
-
cells) at 36 days up to6 (from layer Vcells) at 90 days -
;
3 (from layer V --
.-
-
-
-.
-
l.l.
-
-
-
-
-
2--8 @I (areas 17, 41) 4-6 $Urn (auditory cortex) upto 1Opm (postcruciate gyrusi -
-
ss cortex: 6-8 -
I (continued) -.
41. Lateral habenular nucleus of cats’ 4’ Oval nucleus of neonatal Torpdonturmofafu(elactric Iish)midventral, rostra1 tneduIlaz5 43 Where looking: basal gangliae”.”
39. Nucleus reticularis thalami ol cat (dorsolateral zone)‘” 44-l. Olfactory bulb in adult and newborn cat73
Other
(b) Primary motor cortex of human64~7s
cerebellumof lo-day-old rat (6 days after transplant)’ 1 38. Primary motor cortex and visual cortex of (a) cat, monkey, mouse, rata? (Data applies to motor cortex)
Areu
TABLE
Small and large class
3- 4, up to Elongate IO-12 Reticularis Mitral cells (long secondary dendrites, 2-dimensional bundle in rostrccaudal plane) Medium-sized
Giant pyramidal Varies, up to 6 IO (cat) cells of Betz and large solitary cells of Meynert (layer V, basilar dendrites). (no stellate or other nonpyramidal cells contributedendrites) 3-g Giant pyramidal cells of Iktz(basilar dendrites) and V and VI layer pyramidal cells (basilar and apical dendrites)
-
‘common’
fKl 70’!,,
.__.
per bundle
_.
enter. bundle
neur*ns
dendrites per bundle
.._ --_no Dendrites
NO.
No.
._
I2 4O/cni
dicmefer
Blmdle
400-500 !rm -.
Elm
Several thousand
IenRRth
Bundle
._._
3 14/m
‘.
8/(m)
(90 0;
o/dendrite
50 jt m several hundred /lrn
_
Several mm
_. ..-
while in bundle
Length
l-3 ,ftm to -. 7-g ,drn (cat)
diameter
Dendrite
z P
3. YeritraI horn (h&xi VU, V1IlandZX)ofCz-Ce,T1, T6,“T12,L1-L7,51,520fSpinal cord ofcat (iamina IX only in enlargements)l” 4. Lumbosacral spinal cord (motor nuclei) ofcaP 5, Lamina IX of LT, SI, SZ, 5s segments of spinal cord of pip4R ‘small extracellular
-
space” -
-
Some: 0.2-Q.5 f*rn gap (separated by thin astrocyteprocesses~. Occasionat&, ptrasma rn~rn~ra~~s ii3 direct ~p~~~$~t~o~,
-
5th mo., bundles fuliy developed arid behavior compkte, Also electromyogrdms done. -
II (continued)
--
13. Brain stem reticular
core of cat (bundles beet devrl,opedinme’dial2i3 medullary and; pontine tegmentum)“!l
...-
-
_~
-...
_-..
Longest of large cells: 150@ 2oQo /Lm; of mediun~cells: 600%IOOO~rn!
19 &_.Lateral motor nucleus of C:i~~Cc segments of spina; cord of fetal mouw””
10. Ventral commissure of cervical and lumbosacral spinal cord of cat’” 11. Carnina IX of Tha-Thin segments of spinal cord o f ca~“s,zo
ofratcalso bundtesin ventromedial and dorsolateral regions of ventral horn, but bundles smaller)~’ 8. Lamina IX of cervical to ~~ lumbosacrai spinal cord of raP 9. Ventral horn of cervical enlargement of spinal cord of kittenGY
TABLE
Many Man)
01
: c I rrm : no spaceeeen
widelji’
close together
scattered
‘lying
Many : nil spaceseen withiight microscope
rcntia) More often: separated slightly by astocytic cytoplasm sheet.
-.._
-
-
but in adui:
Yet present at hicrh
Present at birth, need treading reflex of anterior extremities when kitten starts to suckle. Present al birth
~~
-
E
raphe (B /) in -mesencephalon ofsquirrel monkeyls (b) l.ocus coeruleus of squirrel monkeyIs (c) Pars compacta and pars -reticulataofsubstantia nigra, mesencephalon ofsquirrel monkeyI 1.5. Cranial nerve nucleiti3.G’ -16. Nucleus of oculomotor --nerve of catgl
-
18. Somatosensory cortex of rabbit and cat”tmz4, rabbit alone*4J”s47, cat alone”’
19. Visual cortex of rabbit -and of cat”“, rabbit aione13s r5, cat alonegl
--‘-
17. Somatosensorycortex, auditory and visuaf cortices ofratandcat(dataapplies to Krieg’s area 3 of SS cortex of ratP
Cerebral cortex
14. (a) Nucleus
0.3 pm to :.6 pm,ave.: 1.3 /tm(area parietalis, rabbit) -
-
-
-
-.
Order of 50 /dm(rabbit)
-
Some: ‘separated by the extracellular space only’
-
-50 jrm. -(Between large clusters, N 150 pm.) Since apical tufts and basilar dendrites spread N lOO~~,must intermingle with those in adjacent bundles.
-
Direct membrane apposition ‘not infrequent’ (1)12-14nm,sometimes 7-9 nm (2) Often desmosomal junctions (2530nm) (Oftenelectron-dense material)
Occasionally, ‘fairly extensive.’ Frequently, few microns.
-
-~
-
-
Columns: SI cortex,rat, .50O,~,,x diameter Auditory cortex, cat, 100fim diameter, centers separated 150 pm Visual cortex, 350&m diameter Barrels: mouse, LOO-38O~mdiameter (see ref. 55 for refs.) -
-
-
-
-
human and
W-
‘Very
often’
contact.Othcrb:
IXnm
in direct
/Irn
: 76.4/m, pheries: 53.
I /lm
between peri-
centers
Ave. between
- 80
pole,area
cortex, primary visualcorle.\ c .Y
1 of SS cortex, auditory
offrontal
offrontalpoleofcat’~
torycortex,SScortex,corte.x
audi-
gyrus, primary
visual cortex, primary
Postcruciate
cortex)
(auditory
;ortcx
of rat parictai
bundles
ship between barrelsand
50 70/m
No apparent spatial relation-
‘barrellield’ofrat17
-.
process
odor and suckling
Neonates have bundles _ relationship between
cortex of frontal pole. and
(auditory).
visual cortex)
_
Lcral microns
Sometimes
5 15nni
4,17(visua1),4i
long
30 40!cm(rat
-
-
-
Very
Krieg areas 2.3 (SS cortex).
macaque cortex”” Visual cortex ot rat”’
7 and4Oof
T
of
areas 4. 17,
17, visual cortex
Brodman’s
rat*e
Area
monkcyXn
cortex of rhesu\
Motor
ofcat’,.‘,’
cortex
bundle\)
toassume’
Motor
28. Cortex
T. i.
26.
‘reasonable
seeingdendrite
but
cortex of
rat86*s7 (not defnitc.
Somalosensory
-
35. Visual cortex of human fetal brain (34 month-old)4” 36. Cortical pfateoflatef19Zlday) fetal rat cortex56 37. Dorsal developing neocortex of 8 day-old rat embryo, transpIantedintocerebellum of 1O-day-old rat (6 days after transplant)rr 38 Primary motorcortexand visual cortex of (a) cat, monkey, mouse,rat”g (Data applies to motor cortex) (b) Primary motorcortcx of humane’.7j
-
33. Barrel field, parietal cortex, striate region in mouseaa 34. Sensorimotor cortex of albino rat76
-
Circular domain, diameter
.-
-
-
-
--
-
32. Barrel field and area parietaiis of mousetB
29. Cortex of frontal pole, SS and auditory cortices, primary visual cortex of humant? 30. Opossum neocortex17 31. Barrel field of mouse96
2 mm
-
-
IO--20 nnl, frequently nothing bctwccnmembranss
-
-
-
-
4 days after birth : loose bundle-likeorder 24 days : bundies clearly visible Number dendrites per bundle incrcascs with age (see ‘No. dendrites per bundle’)
-
-
-
-
-
-
-
-
_-
Bundle dendrites located preferentially in sides and in areas between barrels Bundle dendrites located preferentially in sides and in areas between barrels -
W
I=:
TABLE if (continued)
itlld
cat48
3. Ventral, horn (lamina VU,, VXlf and IX) of CZ-C~,TJ,TE,LI-L7, S1,Sesegments ofspinalcord ofcat (lamina IXonlyinenlarg~:rmeotsf’” 4. Lumbosacral spinal cord (motor nuclei) of cat4” 5. Lamincz IX of L7, S1, SQ, Sa segments of spinal cord of pig”* 6. (Yentralateral) ventral horn of tunbar(LI)spinalcordofrae (2 groups c&bun&s: (i j Lateral and(2) ~e~ial,ru~nin~~er~endic~~ariy~~ 7. (Ventrolatcral)ventral horn of lumbar(Le)spinalcordafrat (also bundles in ventromcdial and donolateral regionsofv~entral born, but bundlessmuIler~i~ 8. Lamina lXofcervicat to lumbosacral spina! cord of rats L
of spinal cord of
b!.Jdk
(I) Sparsity of myelinated axons in bundle region (2) ~e~drodendr~~~c contacts observed ; symmetrical electron-dcnsesubstanse present (EM) (dcstnasomal) See Area 1,Feature 2. Fewer myelinate~ axons in bundle region Dendrites occupy 55 % volume bundle neu~~p~i
-
Bundlesvery prominent in ~~r~n~cnervenucl~us and pudendal nervesand in ventral andlateralreyions of lateral motoneuronal cell group in CWTi and, somewhat, L&r ‘Might,’ be bundles
Dendritesfromcellsofdifferentmotorcell columns can be insame bundle See Area I ~feature 2
$3)
(I) Individual dendrites afsinglecell may enter different bundles (2) Bundle gainsand loses dendrites along length of
Spinal catecholamine nerve terminals from locus coeruleus after being lesioned witRO-hydroxydoGamine intracisternally, regenerate ‘as ifgrowth was guided by the longitudinally runningdendritic bundles of the nmtnneurons’.
monkey~~z6~8
2. Lamina IX of LF, L7, Sr segments
spinal cord of cat
1. Ventral born of Iumbosacral
-
No direct evidence-may of hind ~~rnb
he involved in rnove~~c~~t
‘. , . non-synaptic information transfer between neurons is predictable’. Doubtsroleincentral programmingofhind limb activity since onfy see bundles in Lc (M/hi& does not inner\iate that region much)
Synchronization _t Matthews thinks closeness of dendrites leads to synchronization of those neurons by ahering t~~res~old e~ha~t~c~I]y
‘Integrative subcenter for sphal effector activity’ Source for program for reciprocal activity of leg muscle pairs in walking, etc.
_^~
14. (a) Nucleus raphe dorsalis (B7) in mesencephalon of squirrel monkey’” (b) Locuscoerulcusofsquirrel monkey18 (c) Parscompactaand pars reticulata of substantia nigra, mesencephalon of squirrel monkeyIs 15. Cranial nerve nucleW6t
13. Brain stem reticular core ofcat (bundles best developed in medial 2/3 medullary and pon tine tegmenIumeY~)
H&n stem
segments ofspinal cordof fetal mouse(Je
12. Lateral motor nucleus of C:,--Cc
of spinal cord of cataevz9
1I, Lamina 1X ofTh~--Thl~scgmentr
10. Ventralcommissureofcervical andlumbosacralspinalcordofcatiz
9. Ventral horn ofcervical enlargement ofspinal cord of kittena
Area l..”_-... ---.I.
TABLE Xl1 (continued) _~--~X__-.--_“..~~.
~_~
(I) See Area I, Feature 2 (2) Bundles surround large fascicles ofrostrocaudal axons (3) Dendritesoften windaroundeach other, increasingchanceforcontact l3undlesinsamelocationsalsofoundinrat,cat,rabhit and rhesusandstumptail monkeystT t,using Falck .Hillarp and glyoxylicacid methods)
..--
(2) (3) (I) (2)
( I)
(2)
probably synapses Most obvious bundling in ventromedial or ventrolateral areas ofventral horn (corresponding to most proximal parts of limb) Bundles include dendrites from medial and lateral moto~uron pools. Also from agonist and antagonist function muscle motoneurons. Also fromcontralateral motoneurons. See Area 1, Feature 2 Bundles perpendicular to long axis ofcord See Area I, Feature 2 Mainly dendrites from distinct cell groups in same column, but some from other groups and from neighboring columns.
( I) Clusters of boutons frequent on or near bundles -
F%mm?s
~__ fmndh function --
Programsitesfor rhythmicrepctitiveoutput like respiration, rest--activity cycle,etc. : override control for autonomous function. Possible Sudden Infant DeathSyndrome role---Seelntroductionandref. 58.
Lack of monosynapticconnections between motoneurons in the contralateral ventral horns: doubts Scheibels’ suggested function of regulating’alternating functionsoftheextremities’ -
Program site for ‘reflexive response sequences involving pairs ofextremities, such as stepping and walking’
Program site for ‘reciprocal activity of leg muscle pairs in coordinated motor activity’
Suggested
of oculomotor
nerve
of rhesus monkeys”
23. Area 17,visual cortex of rat’” 24. Brodman’s areas 4,17,7 and 40 of humans and macaque cortex”5
22. Motor cortex
19. Visual cortex of rabbit and ofcat’“: rabbit alone1 ‘,13, cat alom+ 20. Somatosensory cortex of rat8G,8i (not definite but ‘reasonable to assume’seeing dendrite bundles) 21. Motorcortexofcat’.“.j--7
18. Somatosensory cortex of rabbit and cat?” .1-1,rabbit alonel-l.1.5,ii, cat alone”’
17. Somatosensorycortexofauditory and visual cortices of rat and cat (data applies to K&g’s area 3 of ss cortex of rat)jj
16. Nucleus of cat”’
group
-
Synchronization
Maybe
-
forms
of neurons
of bundles column
They find dendrodendritic contacts which they CI ) Neurons tend to lie beneath each other consideras basisforclcctrotonicinteraction (2) Betzcell,when present,isincentcr within a column. (3) Dendrites tend to twist around each other (4) Upper layer V and lower layer III, more dendrites join bundle (5) See Area 1, Feature 2 (6) Between dendrites, perpendicularly, run small RXCUIS forming synapses with the dendrites (7) Dendrodendritic contacts identified Associates degenerating thalamocortical terminals with bundlesin layers 1Vand 111 (quarltitativc~turly), located more frequently where more apical dendrites are. -
f I) Cell bodies grouped below dendrite bundle that bundle dendrites and neurons havecommon afferentinput since EM observations show concentration of small unmyelinated axons and terminals surrounding bundles (synapses) (3) Layer III pyramid&join bundlesfromlayer V pyramid& (I) Bundling looks different in different regions: Cat visualcortex vs rabbit or cat SS cortex (see Fig. 1I) (2) First bundling ends when dendrites bifurcate in layer Ill/l1 but canreformwithlayerIII pyramidal dendrites (3) See Area 1, Feature 2 (4) Bundle dendrites convcrgc in upper third of layer IV (rabbit) Cat visual cortex: numerous small cell processes near the bundles Bundles run from layer V 10 layer II, arborize in II, III and IV
not as ‘extensive nor so well organized’into as in other parts of brain
(2) Likely
Bundles bundles
$11 (continuedf I.-._. -_----_-._
Cortical plate of late (IV 31-da) J klal rat cortex”’ Dorsal developing ncocortcz ol !&day-old rat embryo. transplanted into cerebellum of IO-day-old rat (6 days after transplant)”
Visual torte\: clt’human fetal brain I 3. 4 month-old) ‘:I
. .-.-... -.
Ifpyramidal cells were proupcd together, their dendrites grouped into bundles. Isolated cells did not rend to habe dendrites group. So bundle formation may depend on grouping of pyramidal cells (in development) and other developmental cwnts.
-
_._ ^_.
_
cortical regions. Auditoryandvisualcorticessimilarincats. Postcruciategyrus: more dendrites(thickcr also) per bundle than auditory or visual cortex.
Bundling differs in different
_-_
Features
-....-. .1 .--~.-.
Visual cortex of rat”’ Kriegarcas 2,3 (SS cortex), 4, I7 (visual),41 (auditory),cortexof frontal pole and ‘barrel field’ of rat’? Postcruciate gyrus, primary visual cortex,primaryauditorycortex, SS cortex, cortex of frontal pole of cat” Cortexoffrontal pole,area 1 0fSS cortex,auditorycortex, primary visual cortex of macaque”. Cortex of frontal pole,% and auditorycortices, primary visual cortices, primary visual cortex of human” Opossum neocorlexli Barrel field of mouse!“’ Barrel field andarea parietali< of mouseL:) Barrel field, parietal cortex, striate region in mouse?:) Sensorimotor cortex of albino rat”’
Area
TABLE
-
Bundleslinked to formacolumn corticalaxonsanda\oncollaterals.
by \crtic‘al intra-
.-__... __-- __..I .._ .. ..._. ..I _^ .___. _~~__._. ,._ Suggested brrudfe ,fhctim
a
nuclei) of calA*
perpentlicularly)~
(I) lateral and (2) medial,
regions of ventral horn, hut hundles smallerIJ1 Lamina IX ofcervical loh~mhos;~cral \nir.al curd 01 r;il ‘.
(Ventrolatwll) ventral horn of lumbar (La) spmel cord or rat talso bundles in vcntromedial and dorsolatcral
running
~,i rat (2groupsofbundles:
5. Lamina1Xof1.7,S~.S2,S:~segments0fspinnlc0rdot‘~igi’~ hornoflumbal (Lo)
IX only in enlargemenl~)~’ 4. Lumbosacral \pinal cord (motor
IX)ofc‘~ C‘s,‘l‘l, 1‘0, 3 ventral l~orn(laminaVI‘I.VIIland 1’12,1,! I.;, S,, Sz segments of 5pm;1l chord cd cat (lamina
ca14*
hornoflumbosacralapi~lal cord ofcat and monkCyl’:.“H 2. Lamina IX IIF 1~6, L:, SI aegmcnts of spinal cord of
I. ventral
Modified Golgi
Rapid Golgi, modified
)
modification
(I’) Mallory-Heidenhain or (g) Methylene blue-azure II Uranyl acetate and lead cltrale (a) Methylcne blue or (I-P)Toluidinc blue Alcoholic uran~l acct.~tc and lcad citrate Cl-alck H~llarp :lu~~re~cer.cc histx?xx~~iatr!
tc) Luxol fast blue.-cresyl violet or Cd) Weil (for myclin sheath) or (c) Cresyl wolet (Nissl) or
Niwl -. complex ethanol ditrercntiation (a) Rapid GoI@ and Golgi C‘ox tungstate (b) Hematoxylin and eosin or
or
roluldme blue ormethylcnc blue. L‘rcs>I violet (Niwl), huffe~ed thionine. Holmcs\ilwr. or paraflin hauta or Held Auerbach Urunyl acetate and modified lcad citrate
LM
(a) 0.5 7, toluidine blue or (b) alcoholic solution of p-phenylet~cdiamine Uranyl xeta~e and lead citrate Harris hematoxylin Ponccau red lipht green
LM LM
EM
LM
TM LM
LM
Rapid Golg~, modified
-i-
cr
0
mouse”’
Barrel field, parietal cortex. striate region in mouse?:’ Sensorimotor cortex of albino ratTR Visual cortex of human fetal brain (.3 -4-month-old)‘!’ Cortical plateoflate(l921-day)fetal rat cortex””
parietalisol
zone)“’
43. Where
looking:
basal ganglia”:‘*” .._ . . _ _ ._..^, _.-._.-
.._. _
41 Lateral habenular nucleus of c&; 42. Oval nucleusofneonatal 7'urpedo/f,ar,,lurrrro (clcctriclish)midventral, rostrai medulla’j
39. Nucleus reticularis thalami of cat (dorsolatcral 40. Olfactory bulb in adult and newborn cat;,’
37. Dorsal developing neocortex of X-day-old rat embryo. transplanted intocerebellum of IO-day-old rat (6 days after transplant)” 38. Primary motor cortex and vihual cortex of (a) cat, monkey. mouse,raW (Data applies to motor cortex) (b) Primary motor cortex of hurnanb-‘,‘-
33. 34. 35. 36.
32. Barrelfieldandarea
30. Opossum neocortex17 3 1, Barrel field of mouseB’;
.________..__ “.l._
modifid
(b) Rapid Golgi, (not given)
Rapid Golgl. modllicd Rapid Golgi. modified (not given) Rapid Golgi and Gotgi- Kopsch sllvcr impregnarion methods Golgi by chloral formaldehyde procedure and toluidine blue Uran) t acetateand lead citrateand Sodium acetate bullicr and uranbl acctatc in \odium acctntc (not given) -_,___._ .._. _~
modified
Colgi,
LM 1.M EM LM LM EM
1-M EM
EM LM
LM
LM
LM
LM
Miwasrop~
1.M
-.__.
(a) Rapid
___-___
_~-~---.~______,_“~
LM EM LM EM 1.M L.rM ;Illd f PI1
_-.
(a) Toluidine hluc or (b) Nissl or (c) Cajal (not given) (a) 1 “/0 uranyl acetate in 70”, methanol or (b) Totuidine blue Lead citrate (a) Alcohol solution of toluidinc blue or (b) Hematoxylin-eosin or (c) Luxol fast blue and PAS rcactlon or (d) Bodian, modified (Luna) (not given) Gotgi-Cox (Ram&-Moliner modification) Freez-fracture,(etchingon some): then platin,~,~~--carb~~~~
(a) Toluidine blue or (b) Nissl or (c) Cajal Toluidine blue
.-
27. Postcruciategyrus, primary visual cortex, primary auditory cortex, SS cortex, cortex of frontal pole of cat’? 28. Cortex of frontal pole, area 1 of SS cortex, auditory cortex, primary visual cortex of macaque” 59. Cortex of frontal pole, SS and auditory cortices. primary visual cortex of human*i
-1 Slaining techniyue __“.
IV (continued)
Avea _._~~~~.-
I’ABLE r3 f? __
Fig. 1. Cross-section of a dendrite bundle in lamina IX of cat lu~lbosacral spinal cord. Dendrites DI and Dz are kept apart by an astroglial process Aereas Da and D.I seem directly apposed. i: 4680. (From ref. 48.)
In addition
to the spinal
cord,
dendritic
bundles
are found
in the reticular
formation of the cat”“. Bundles may include as many as 15 dendrites, with shafts joining and leaving the bundle along its length. The dendrites in bundles tend to surround large fascicles of rostrocaudal light microscopy) between the dendrites
axons. There is often no space resolvable themselves, and the separation is usually
(by less
than I /fm. Frequently, the dendrites twist around each other, making possible contact between them more likely. Bundles are not present at birth (Fig. 4). As previously noted, Scheibel et a1.63 suggest that the role of bundles in the reticular formation may be to act as a program site for ‘rhythmic repetitive output’ such as respiration and the rest-activity cycle. Bundling has been observed among the dendrites of the serotonergic cells in the nucleus raphe dorsalis, the ~loradrener~ic neurons in the locus coeruleus, and the dopaminergic cells in the pars compacta and pars reticulata of the substantia nigra of the squirrel monkey18 as well as in these locations in the rat, cat, rabbit, and rhesus and stumptail monkeys’“.
250
fetal
Id 4m
Fig. 2. Drawings of horizontal sections through the ventral horn of cat spinal cord at approximatclg LS Sl segments, showing development of motoneuron dendrites and dendrite bundles. In fetal cord, dendrites have radial distribution. At 1 day of age dendrites begin to show sagittal organization. At 12 days bundles are beginning to form at a, band c. At 4 months the motoneuron system is essentially mature and dendrite bundles at a, b and c arc well-developed. Neurons A, B and C contribute dendrites to more than one bundle. Other abbreviations: vm. ventromedial white matter: VI. ventrolateral white matter: d, a small bundle of commissural dendrites, which are apparent at even one day of age. Inset diagram shows plane of section and spinal laminar organization of the relevant area. Rapid Golgi
variant. (From ref. 74.)
251 Bundles have been identified Tredici et al.9’ in the nucleus form a hundie. separation
Direct
of the oculomotor
membrane
to desmosomai
in cranial
contacts,
apposition
nerve nuclei by Scheibel et al.64 and by nerve of the cat, where 3-5 dendrites is common,
often with electron-dense
ranging
from
material,
a 7-9 nm
of 25-30 nm
separatiorP.
Fig. 3. Drawing of horizontal section through the ventral horn of 3-month-ofd cat spinal cord at L5-Sl , showing Iongitud~naJ and horizontal dendrite bundles. A, C, E and F are rnotoneurons; B and D, spinal interneurons; a-f, dendrite bundIes crossing midfine as part ofcommissural system; g and h, ~ong~tud~nai dendrite bundles; i and j, dendrite tips protruding into ventrolateral white matter; k, tips of dendrites forming commisrural systems ending in ventral grey matter. Rapid Golgi variant. x 150. (From ref. 72.)
Fig. 4. Cross-sections through the dorsal half of the lower medulla oblongata in newborn and adult cats, showing the difference in dendrite organization of reticular neurons. In the rostra1 part of the nucleus reticularis parvocellularis, A, and the nucleus reticularis magnocellularis, B, of the newborn, neurons have radiating dendrites. In the adult, dendrites have formed bundles surrounding the rostrocaudal running fascicles of myelinated fibers. Other abbreviations: C, medial longitudinal fasciculus; D, nucleus prepositus hypoglossi; E,medial vestibular nucleus. Drawing: x 100. Rapid Golgi variant. (From ref. 74.)
2.3. Orher awas
The Scheibelsi” have found bundling in the dorsolateral zone of the nucleus reticularis thalami of the cat (Fig. 5). Here, the number of dendrites per bundle varies from 3-5 up to IO- 12, with 60-70 % of the dendrites in the area involved in bundles. The bundles gain and lose dendrites along their length of 400-500 ,um. Again, the separation between the dendrites is frequently so small as to be unresolvable by light microscopy. The bundles are not present at birth, but become progressively more obvious in the first 30-60 days of life. Because of its location, the nucleus reticularis thalami is crossed by almost all of the fibers connecting the thalamus with the cerebral cortex. There appear to be synapses between these fibers and the cells and dendrites of the nucleuss. It is thought that the nucleus serves as a feedback system, gating thalamocortical interaction by imposing tonic and/or phasic inhibition on thalamicneuronss5@j. Recent neurophysiological studies appear to support these notions”. The Scheibels suggest the bundles as possible programming sites for tuning and modulating the rhythmic slow wave processes in the thalamus and cortex.
253
Fig. 5. Drawing of horizontal section through dorsolateral portion of adult cat nucleus reticularis thalami at approximately AIO. Dendrites of many reticularis neurons (nR) form bundles (e.g. at b). Other abbreviations: f, fascicles of dorso-ventrally running axons; VB, ventrobasal nuclei; VL, ventrolateral nuclei; Cd, caudate nucleus; Hy, hypothalamus. x 300. Golgi variant. (From ref. 70.) Dendritic
bundles
the cat73. Dendrites
its course
and
are present
originating
are very tightly
in the rostrocaudal
from
the mitral
packed,
plane
of the olfactory
cells join and leave each bundle
as seen by light microscopy
bulb of along
and electron
microscopy. The bundles in the olfactory bulb are present at birth, and it is suggested that through their role as the programming site for ‘stereotyped, routine or repetitive types’ of output, the bundles are necessary in the relationship of odor to suckling behavior. Bundles have also been observed in the lateral habenular nucleus of the cats’. In animals other than mammals, bundling has been observed in fish, specifically in the oval nucleus of the neonatal Torpedo marmorata25. Close apposition of membranes (8-10 nm apart) and some desmosomal contacts (~20 nm) are commonly present. Many axodendritic synapses are observed between the bundle dendrites and the small axons that run perpendicularly to the bundles. 2.4. Cerebral cortex In the cerebral cortex two types of bundling have been found: (1) amongst the apical dendrites of layer V pyramidal cells (Figs. 6 and 7) and (2) amongst the basilar dendrites of the giant pyramidal cells of Betz and the large solitary cells of Meynert in layer V of the primary motor and visual cortices (Figs. 8 and 9).
III
Fig. 6. Drawing of four layer V pyramidal cells whose apical dendrites form a bundle. From a Colgi preparation. (From ref. 55.)
255
Fig. 7. Dendrite bundles in cat visual cortex. Top left: Frontal sections, x 200. Top right: Bottom: sagittal section showing bundle cross-sections. x 800. (From ref. 21.)
x 800.
256
Fig. 8. Comparisons of basilar dendrite patterns of medium-sized pyramids, A, in layer III with those of Betz giant pyramidal cells, B, in the fifth layer of precruciate gyrus of an adult cat. Enlargement of a bundle segment is shown at C. Rapid Golgi variant. (From ref. 74.)
2.4.1, Apical dendritic bundling
Peters and Walsh55 and Fleischhauer et al.24 were the first to report bundles formed of apical dendrites in the cerebral cortices of the rabbit, cat, and rat (Fig. 6). Peters and Walsh studied the somatosensory, auditory and visual cortices of the cat and rat. The data given in their paper applies to Area 3 (Krieg) of the somatosensory cortex of the rat. The bundle size ranges from 4-6 dendrites of the layer V medium and large pyramidal cells, up to about 14 (Fig. 10). SzentagothaissJss, including the layer III pyramidal cells in the bundling, states that there are approximately 20-30 neurons involved in each bundle. The bundling disappears in layer 11 through dendritic arborization and bundle merging. Peters and Walsh find that the cell bodies are grouped below the dendritic bundle. The distance between the bundles is typically of the order of 50 pm, while between the larger bundles it is approximately 150 pm. The authors point out that since the basilar dendrites and apical tufts spread horizontally for approximately 100 pm, there must be some overlap with those in the neighboring bundles. It is also noted that columns in the somatosensory cortex of the cat have a diameter of the order of 500 pm, i.e. bundles are not columns (see later discussion on columns). Peters and Walsh think it likely that the dendrites in a bundle (along with the corresponding neurons) share a common afferent input, judging from electron microscopy studies
257
Fig. 9, Drawing near crown of precruciate gyrus, pr, showing the types of pyramidal cells in the six cortical layers. In layers 2, 3, and 5, the pyramids’ basilar dendrites form thick horizontal neuropil fields at a, b, and c. The giant pyramids of Betz in layer 5 generate very long basilar dendrites which form bundles, d. Apical dendrites also may form bundles, e. x 240. From a single section of adult cat cortex. Golgi modification. (From ref. 62.)
show an accumulation of small unmyelinated axons and terminals encompassing a bundle, and synapsing with the dendrites in the bundle. From these observations, Peters and Walsh suggest that perhaps bundles are organizational compowhich
nents of columns. Fleischhauer et a1.21-24,47 and Detzer I4915 studied the somatosensory cortex of the rabbit and cat. They find approximately 15 dendrites (about 6 from layer V pyramidal cells) per bundle in the rabbit somatosensory cortex. Most of the dendrites in the region appear to enter into bundles. The typical bundle diameter (rabbit) is 20-35 ,um. Again, the distance between bundles is found to be of the order of 50 ;l.rn (rabbit). As in the studies of the Scheibels above, it is mentioned that Lhe bundle gains and loses dendrites along its length. The dendrites lie closely together, with some ‘separated by extracellular space only.’ With regard to this, MPrllgard and Mraller50
258
IV,
VA
Fig. 10. Reconstruction of a cluster (bundle) from a series of tangential 1 /cm sections, segmented to show the relationships of the dendrites as they approach the cortical surface. (From ref. 55.j
of dendrodendritic gap junctions between the dendrites in a bundle. Fleischhauer et al.21-24 and Detzer 14115have compared the somatosensory and visual cortices of the rabbit and cat. They find, typically, 2-3 dendrites (from layer V
suggest the possibility
259
8
b
Fig. 1I. Diagram of the dendritic bundling patterns in the visual cortex (a) and the somatosensory cortex (b) of the cat. (From ref. 21.)
pyramidal cells) per bundle in the cat, and about 5 in the rabbit visual cortex (compared to 6 dendrites from layer V cells observed in the typical bundle of the rabbit’s somatosensory cortex). It is found that bundling follows different patterns in different regions (e.g. see Fig. 1 I). Fleischhauer et al.24 propose that dendritic bundling serves to synchronize firing among the neurons involved. Petsche et al. 57 also suggest synchronization as a function of bundles since layer V neurons are connected through bundling to the generator layers 11 and III. Other researchers have also found bundling among the apical dendrites of pyramidal cells in the cerebral cortex. Stahl and Broderson86JJ7 have identified (histochemicaily) what they believe to be bundIes of apical dendrites from pyramidal cells in the somatosensory cortex of the rat which run from Iayer V to layer Ii, arborizing in layers II, III and 1V. Bundling has been observed in the motor cortex of the cat”JJ-7 and the rhesus monkeysz. In the cat there are from 2 to 7 neurons involved in the formation of a bundle. The neurons tend to lie beneath each other; when a Betz cell is present, it is often in the center of the neuron group. The distance between bundles ranges from 50 to 100 pm. Here again, dendrites tend to wind around each other, and the dendrites are frequently in contact. As elsewhere, bundles gain and lose dendrites along their length. Between the dendrites, running perpendicularly, are small axons which form synapses with the bundle dendrites. Babmindra et al .2,3 also identify dendrodendritic contacts. In the monkey motor cortex, Sloper82 associates degenerating thalamocortical terminals with bundles in layers IV and III. In a quantitative study, the terminals are shown to be found more frequently where apical dendrites are most numerous. There is an apparent correlation between terminal location and the number of apical dendrites at that location. He also cites Garey and Powell26 who have found
260 that, in the visual cortex, degenerating
thalamocortical
terminals
seem to be grouped
at about 100 !drn intervals, possibly related to the intervals between bundles found in that region (see results of Von Bonin and Mehler, Winkelmann et al. and Feldman and Peters below). The groups of dendrites Von Bonin
and
Mehler”5
macaque
cortex
bundles. (bundles)
Von Bonin and of approximately
found by Fifkova”O in the visual cortex of the rat and by in Brodman’s
have been reexamined
areas 4, 17, 7 and 40 of the human by Peters and Walsh55 and interpreted
Mehler cite a distance 80 pm.
between
the groups
and as
of dendrites
Winkelmann et al.9’ have found bundles in the visual cortex of the rat. The number of dendrites per bundle averages about 5 in lower layer Vb to about 8 in upper layer Va. The average bundle diameter is given as 26 ,um, with an average distance between bundle centers of 76 /lrn (53 /Am between bundle peripheries). Feldman and Peters” have found bundles of apical dendrites pyramidal cells in :
of’ layer
V
(a) Krieg areas 2, 3 (somatosensory cortex), 4, I7 (primary visual cortex), 41 (primary auditory cortex), the cortex of the frontal pole and ‘barrel field’ of the rat: (b) postcruciate gyrus, primary visual cortex, primary auditory cortex. somatosensory cortex, and the cortex of the frontal pole of the cat; (c) area I of somatosensory cortex, auditory cortex, primary visual cortex of the frontal pole of the macaque and of the human; and (d) neocortex of the opossum.
cortex,
and
They find 6-8 dendrites per bundle in the rat’s somatosensory cortex, with a distance between the bundles in the rat’s visual cortex of 30-40 pm. They see no spatial relationship between the barrels and the bundles in the rat’s parietal cortex. The separation between bundles in the cat’s auditory cortex is estimated as 50-70 pm. Feldman and Peters, like Fleischhauer, note that in the cat bundling patterns differ in different regions, e.g. the postcruciate gyrus has more dendrites per bundle than the auditory or visual cortices, but that the auditory and visual cortices are similar. Whereas Feldman and Peters observe no relation between the barrels and bundles in rat parietal cortex, Whites6 and Detzerta, who have studied bundles of apical dendrites in the barrel field of the mouse, both find bundles of dendrites located predominantly in the sides of, and in areas between, barrels. Fleischhauer and DetzeF also observed bundling in the barrel field, parietal cortex, and striate region of the mouse. Schierhorn’s
studied the development
of bundling
of apical dendrites
of iayer V
pyramidal cells in the sensorimotor cortex of the albino rat. He finds that by 4 days after birth a loose bundle-like order is observed. By 24days after birth, dendritic bundles are clearly visible. At 36 days there are about 3 dendrites per bundle; at 90 days there are up to 6 dendrites in a bundle. The dendrites appear entangled, possibly allowing more contact
between them. processes in the Bundling has been found by Ms11gard49 among the neuroblast visual cortex of the (3-4-month-old) fetal human brain. Msllgard identified dendrodendritic gap junctions amongst the processes as well. It is suggested that bundles
261
Fig. 12. Betz cell (b) with a primarily cylindrical dendritic domain. The group of pyramidal cellsat aare to be centered on the + in the dendrite domain in b. Many of the apical dendrites of the group of cells appear to form bundles (c) with the descending dendrites of the Betz cell. Section cut perpendicular to surface. (From ref. 75.)
could be electrotonically coupled (by dendrodendritic gap junctions) units which came from neuroblasts lined up in the same vertical row. Peters and Feldman56 find no evidence of bundling of the apical processes of immature neuroblasts in the cortical plate of the 19-21-day-old fetal rat cortex. However, the beginnings of bundling appear among the dendrites of more mature nerve cells. Dasll observed bundling in the dorsal developing neocortex of the 8-day-old rat embryo transplanted into the cerebellum of a IO-day-old rat. If the pyramidal cells were grouped together, their dendrites grouped into bundles, with entire dendrite lengths in one bundle. Das suggests that bundling may depend on the grouping of pyramidal cells and other developmental events. 2.4.2. Basilar dendritic bundling The basilar dendrites of the giant pyramidal cells of Betz and the large solitary cells of Meynert in the primary motor and visual cortices have been found to form bundles in the monkey, cat, mouse, and rat62 (Fig. 8). In human motor cortex64975 (Figs. 12 and 13) the basilar dendrites of Betz cells form bundles with the apical and basilar dendrites of other pyramidal cells. The results in ref. 62 are given for Betz cells but also apply to Meynert cells. The number of dendrites (of Betzctlls) per bundle
Fig. 13. Betz cell (b) with large dendrite angling downward into pyramidal cell groups. Dendrite shaft and branches form bundles with the pyramidal cell basilar dendrites. Section cut perpendicular to surface. (From ref. 75.)
varies, ranging up to 6-10 in the cat, 3-8 in humans. About 50”/, of the bundles in humans have one dendrite from a Betz cell (identified as the dendrite profiles with diameter of more than 8 ,um; some of the smaller profiles may also be from Betz cells). In 7 out of 24 bundles, 1 or 2 smaller dendrites partially encircle a large dendrite, possibly increasing the chance for contact. In general, the dendrites are separated by lo-20
nm in the human,
frequently
with nothing
between
the membranes.
As in
bundling in other regions, dendrites may join or leave the bundle along its course. The bundles are several thousand /Am in length, with a diameter (in humans) of 12-40 pm. As the basilar dendrites of Betz cells spread to a 2 mm diameter circular field, the authors
point outs” that 4 giant cells can lie along the basilar dendrite
of one cell
(the distance between cells averages 240$45 pm). Bundling between thecells’dendrites could possibly bind a column (see discussion on columns below), roughly defined by the dendritic field of one Betr cell, to other columns. It is also suggested62 that bundles might serve as the location of programming for ‘sequencing and modulating phasic discharge patterns of Betz cell complexes.’ From the human study, it is proposed that, with age, the decreasing number of horizontal dendrites may lead to ‘progressive diminution of central program storage areas.’ 2.5. Comparisons Few comparisons
can be made of these neuroanatomical
results as studies have
263 seldom
been done in the same brain
lamina
IX of the cat spinal cord we can compare
and (2) Matthews
regions
with quantified
results.
Of the few, in
the results of (1) the ScheibelsGT,68
et aL4s:
5-20 20-60 jrm 1OO-several hundred [rm 0.2-0.5 jrrn and occasional direct membrane apposition (electron microscopy)
3-25
Number of dendrites per bundle: Bundle diameter: Length of dendrite while in bundle:
I O-70 I’m 400-600 /trncR (500-700 (lrnGT) 2 I’m or less (light microscopy)
Distance between dendrites in bundle:
In addition to these results, which are fairly consistent, both researchers observe that a bundle gains and loses dendrites along its length. In lamina IX of rat spinal cord, we can compare the number of dendrites in a bundle found by Anderson
et a1.l and by Kerns and Peters41 (about
1200-1600 vs over
1400), and we can compare values for bundle diameter (largest, 910 pm vs 2.50 pm). In rat somatosensory cortex, we have the results of (1) Peters and Walsh55, (2) Feldman and PetersIT, (3) Schierhorn ‘i6, and (4) Stahl and Brodersonss,s7:
Number of dendrites per bundle: Dendrite diameter:
(1)
(2)
(3)
(4)
4--6 up to 14 3-8 jlrn (layer IV)
6-8
-6
-
-
3-5 ,um (min.)
In rat visual cortex the distance between bundles is 30-40 pm as measured Feldman and Peters17 and 76 pm, according to Winkelman et a1.g7. 3. PHYSIOLOGICAL
Although
MODELS
dendritic
bundling
has been found
experiments throughout the brain, determine the undoubtedly important we presented
by
several possible
function. In this Section, physiological models.
in numerous
neuroanatomical
there have been no physiological studies to functions of this bundling! In the Introduction,
physiological
we discuss,
roles that bundles
in a little
more
detail,
might
play in brain
several
aspects
of
An important first point is to clearly distinguish between bundles and columns. Bundles are in genera1 smaller than columns; Peters and Walsh55 suggest that a group of bundles may form a column. For completeness, we briefly discuss some aspects of columns, which are not observed anatomically, but are seen through their physiological function, in contradistinction to the situation for bundles. For more detail on columns, see the recent review by Mountcastless. 3. I. Columns The cerebra1 cortex
appears
to be organized
in columns
of lOs-lo4
intercon-
264
\
Fig. 14. Idealized model of striate cortex with two orientation hypercolumns (each 180”) and two ocular dominance hypercolumns. Columnar walls are actually not flat and the intersections not strictly perpendicular. R, right eye. L, left eye. (From ref. 36.)
netted cells running through the cortical layers, perpendicular to the pial surface. The column is defined by its thalamocortical afferents and by its patterns of functional response, i.e. all cells in a column respond to the same sensory modality and have roughly the same receptive field. In addition to being a physiologically vertically organized unit, a column is also somewhat anatomically vertically arranged, with primarily vertical connections between the neurons. An active column inhibits the firing of neurons in the neighboring columns, making electrical activity in the cortex even more vertically oriented. Note that the columns are not visible by ordinary histological staining methods, but are identified as physiological units, originally by recording the electrical firing response of individual neurons to sensory input, and more recently by labeling techniques: by transneuronal autoradiography and by the clever [14C]2deoxyglucose method of Sokoloff 40~33. Mountcastle, the first to identify columns, found that the somatosensory cortex has columns with diameters of roughly 500 ,urnsl. The best studied area is the primary visual cortex, where the beautiful experiments of Hubel and Wiesels*-36 have demonstrated that there are two independent partitions as shown in the totally idealized model of Fig. 14. Pyramidal cells in each column yield the maximum number of spikes when the animal is stimulated by short line segments
26.5 (in a given region of the visual field) which have a given orientation and are excited by the left (L) or right eye (R). The dimension associated with an orientation column is ,50 pm whereas the dimension of an ocular dominance column is - 400 pm. Hubel and Wiesel also define hypercolumns which comprise a complete 180” discrimination in orientation (-600 pm) and L-R ocular dominance (-800 pm). A recent studysG has clearly established the grid but shows that the boundaries of the columns are not sharp and regular as in the idealized model of Fig. 14. Goldman and Nauta27 have found columns located throughout the mammalian cerebral cortex, so that we may consider columns as a general organizational feature of the cortex. Mountcastle has recently presented a very interesting organizational model of the brain52. He regards the (macro~olumn) column, of some 500 pm in diameter, as the basic processing unit (with interactions among the macrocolumns~. Each column consists of basic modular subunits of neurons, or minicolumns, roughly 30 pm in diameter, put together in such a manner that the (macrocolumn) column can perform its appropriate processing or memory storage tasks. Although Mountcastle does not make this identification, we propose that vertical dendrite bundles may constitute the minicolumns or basic subunits of the columns he discusses. Shaw and RoneyslsO have presented a specific, testable mathematical realization of the combined organizational ideas of Mountcastle and the learning hypothesis of Hebb30. Incorporating the known statistical nature of chemical transmission at the synapseag, Little and Shaw42,43?79$*1 d eveloped a model of memory based on the Hebb pre-post-synaptic modi~cation hypothesis. Analytic solutions to this mathematical model were obtained showing very interesting behavior. However, in order to obtain a complete, fully interpretable theory, Shaw and Roney were forced to introduce a Mountcastle-like organizational structure! The result was a network of 103-10” highly interconnected neurons, corresponding to a cortical (macrocolumn or hypercolumn) column, which was divided into assemblies consisting of roughly 20 neurons. It was shown that the average output of the neurons in an assembly to a single stimulus presentation to the column was equivalent to the post-stimulus histogram (PSH) of an individual neuron in the assembly, the PSH being obtained by averaging the output of the neuron over - 20 presentations of the stimulus to the column. In response to a ‘meaningful’ stimulus, the network (column) will be excited into one of many different sequences of {averaged) firing patterns in which the activity flows from assembly to assembly. persisting for some fraction of a second. The columns interact directly and/or through thalamocortical pathways. A number of interesting, testable predictions followed. A key input into this theory was the assumption that the neurons in this (subunit) assembly were closely coupled electrically. We suggest that the subunits (minicolumns), or assemblies of this model, are the anatomically identified bundles. Support for this equivalence comes from the likely common afferent input to a bundle suggested by Peters and Walshss, which is consistent with the possibility of averaging taking place within the bundle (which defines the theoretical assembly). The possibility suggested by several experimenters of dendrodendritic gap junctions (see Table 111, ‘Features’) also supports the averaging hypothesis, with the dendrodendritic junctions acting as the coupling mechanism. Schmitt et al .‘i8 suggest bundles as ‘ideally suited for
266
d
B Fig. IS. Summary figureindicating the possible location and substrate for macromolecular coding of stored output patterns. A: model of the extended membrane modified slightly from Lehninger (Pwc. j7af. Acnd. Sci. (Wash.), 60 (1968) 1055-I 101). The neuronal plasma membrane is the dynamic interface between the extraneuronal space, a, and the cellular cytoplasm, b. Its inner zone. c, a liquidprotein complex bears a more diffuse, covalently linked outer zone, d, composed of ohgosaccharide chains, e, capped by negatively charged sialic acid moities, f. B: cross-section through a typical dendritic bundle in cerebral cortex, based on tracings from electron photographs (approximately 20,000 :-). The arrow points to one interface between closely apposed dendrite membranes. C: an hypothesized enlargement of the area noted in B. In the interval between the membranes of two dendrites crosssections, a and b, oligosaccharide-sialic acid side chains extend toward each other, immersed in the hyaluronate rich extraneural space (shaded area). (From ref. 71.)
the interaction
of dendrites
through
extracellular
fields’, which is another
possible
averaging mechanism. Other support for bundles being assemblies is that the typical size of a bundle is of the same order as the size hypothesized for the theoretical assembly. Difficult physiological experiments are necessary to test these assumptions and predictions. For more details see ref. 79. Macromolecular coding of stored output patterns has been suggested by Scheibel and Scheibel~‘~‘~ as a possible mechanism for inscribing central programs within dendrite bundles. It is hypothesized that the intrafascicular spaces within the bundle, and especially those between closely opposed dendrite shafts, provide a sheltered micromilieu affording opportunities for physical interdigitation and chemical interaction among the macromolecular projections (Fig. 15). Cation-mediated linkages established between adjacent polyamines making up the membrane outer surface may operate under increasingly predictable sets of input-output restrictions, the latter possibly repre tented by characteristic patterns of electrotonic coupling potentials. The resultant stabilization of these links associated with large changes in
267 hydration and an increase in polysaccharide concentration could lead to formalization of steric configurations. These stabilized steric macromolecular patterns may contain the coded program determining output characteristics of the dendrite bundle’s corresponding neurons. The actual nature of the coding scheme has yet to be determined. All bundling probably does not serve the same function. In the case of Betz ceils, bundling extends over more than a column’s diameter, In this case, perhaps the bundles perform the task of providing the inhibition between neighboring columns as discussed above, In the spinal cord of the rat, bundles are found to be formed of 1200-1600 dendrites. Great reliability may be the principal function of bundles here. Predominantly, however, there are the smaller bundles of the order of 20 dendrites, with diameters of the order of 50 jcm. In order to determine the functions of bundling, it is necessary to determine whether there is coupling, electrotonic or otherwise, among the dendrites in a bundle. If there is coupling, the bundling could serve as an averaging mechanism, uniting the neurons involved into an assembly, possibly acting as Mountcastle’s column subunit. Firing correlations could be determined between neurons having dendrites in the same bundle and in different bundles. The experiment will require the use of two or more closely spaced extracellular microelectrodes, as in the work of Verzeanosa,93, so as to determine the relevant correlations between neurons within the same bundle, within neighboring bundles, and within bundles in different columns (networks~. In addition the dendrite systems of these neurons would need to be visually identified and their presence in the same (or different) bundle(s) verified. Only the most rigorous speci~cation of dendrite membrane continuity would provide a reasonable basis for the assumption that correlation of firing patterns between neurons might be due to dendritic coupling phenomena. This experiment would also indicate whether firing activity moves from one bundle to another, as discussed above. Another possible experiment would be to determine whether there is a correlation between brain area and the number of dendrites per bundle. Regions with a large number of bundled dendrites (as in rat spinal cord) might be expected to be regions where high reliability is needed. Perhaps a region with a smaller number of neurons is one where greater flexibility and processing or storage capacity is needed. Other interesting experiments would be to further determine the pattern of bundle development in the neocortex (see discussion of bundle development in the neocortex and its possible role in Sudden Infant Death Syndrome above). The development of bundling after birth may possibly reveal significant correlations to learning and behavior. These and other physiological experiments, although difficult, are necessary in order to clarify the role of bundles in brain function. 4. SUMMARY
Dendritic bundles have been found throughout the mammalian brain. Unquestionably, these bundles must serve one or more important, fundamental roles in the brain’s fulictioning. However, no physiological experiments to determine their
268 function
have been performed
the numerous
anatomical
logical possibilities
on these well-established
reports
of bundling.
for the functional
anatomical
In addition,
significance
units. We survq
we discuss several physio-
of bundles.
ACKNOWLEDGEMENTS
Some of the original ported
by USPHS
K.J.R.
is supported
Grants
studies on dendrite NINDS-01063,
by an IBM predoctoral
bundle
structure
NINDS-10567,
by A.B.S. were sup-
HD-00972
and NB-01063.
award.
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pyramidal
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properties
of units of the thalamic
reticular
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