The projection of the somatic sensory cortex upon the thalamus in the cat

BRAIN RESEARCH

369

T H E P R O J E C T I O N OF T H E SOMATIC SENSORY C O R T E X UPON T H E T H A L A M U S IN T H E CAT

E. G. JONES AND T. P. S. POWELL

Department of Human Anatomy, Oxford University, Oxford (Great Britain) (Accepted March 22nd, 1968)

INTRODUCTION

It is now well established that fibres of' cortical origin may mediate effects upon transmission in the somatic sensory relay stations of the spinal cord and medulla oblongataa,6,14,20,25, 54, and there is recent work to indicate that corticofugal fibres may also have an effect upon relay nuclei in the thalamus 5. However, while anatomical confirmation has been forthcoming to support these physiological observations at the lower relay sites33,a4, 55, little has been done in this respect at the thalamic level, the small amount of evidence in the literature stemming chiefly from studies of normal material 49,~2 or from experimental studies using the Marchi technique31,46, 56. the deficiencies of both of which are well known. Recently, there have been a few reports based upon studies made with the more sensitive Nauta technique which suggest that cortical efferent fibres do, indeed, terminate in the nucleus ventralis posterior s,z2,43 and in the posterior group of thalamic nuclei 16,3s. However, many of these observations were made incidental to other investigations and, in addition, at the relatively long survival periods used, much of the axonal fragmentation visible in the thalamus could have represented retrograde degeneration of thalamo-cortical fibres 1~,21,48. It seems necessary, therefore, to make a detailed investigation taking this factor into account and the present paper is devoted to the cortico-thalamic connexions of the somatic sensory and certain related areas of the cerebral cortex. MATERIAL AND METHODS

In 40 adult cats, many of which have been used in other investigations 2a,z°, lesions of varying sizes were placed in most of the known functional and architectural subdivisions of the cerebral cortex, the majority, however, being confined to the somatic sensory or motor regions z4,~8. Most of the animals were killed 6-7 days postoperatively by perfusion with saline and 1 0 ~ neutral formalin. Five, however, were killed after only 3 days when retrograde axonal degeneration could be expected Brain Research, 10 (1968) 369-392

370

E.G.

JONES A N D T. P. S. P O W E L L

to be absent or minimal. Atter a further period of fixation varying from 4 to 8 weeks, during which time the site of the lesion was photographed, the brains were sectioned coronally, horizontally or sagittally on a freezing microtome and a I in 10 or I in 20 series of 25/, sections stained according to the method of Nauta and Gygax 4e. In each case, an alternate series was stained with thionin or cresyl violet acetate. Axonal degeneration was recorded on projection drawings of relevant sections and upon a standard orthogonal reconstruction of the n. ventralis posterior prepared from a Nissl stained seiies of fi'ozen sections. Cortical lesions were reconstrtlcted on tracings of the brain photograph. REsuErs

Before presenting the experimental results, it seems necessary to describe in some detail the basis for our identification of certain of the thalamic nuclei, especially those constituting the 'posterior group', For the purposes of the present study, we have adopted the customary terminology such as appears, for example, in the atlas of Jasper and Ajmone Marsan "-'~ionly in referring to the main thalamic nuclei. Our identification of the posterior group is based in the first instance upon the more comprehensive descriptions in the literature 4°,47,s°,51, together with a personal examination of a number of available brains, both normal and experimental, stained by the Nissl method. The posterior group is, then, a region of morphologically heterogeneous cells embracing the caudal pole of the n. ventralis posterior and extending caudally to gradually merge with the medial geniculate body and midbrain tegmentum. When studied in a rostro-caudal sequence of coronal sections, the group first makes its appearance at about the level of the habenulo-interpeduncular tract where it can usually be seen as two, tenuously-connected elements: one lies immediately dorsomedial to the n. ventralis posteromedialis (VPM), adjacent to the centre median nucleus, and merges dorsally with the n. lateralis posterior; the second is more laterally situated and is intercalated between the n. ventralis posterior, the external medullary lamina and the lateral geniculate body. Slightly caudal to this level, the whole region becomes somewhat more extensive and the two elements are now more obviously continuous. Here the group is applied to the caudal pole of the n. ventralis posterior u.ith which it merges; medially, it is in contact with the centre median nucleus; directly ventral is the medial lemniscus, while ventrolaterally and dorsally, respectively, it shades insensibly into the magnocellular division of the medial geniculate nucleus and the n. lateralis posterior. At a still more caudal level, opposite the posterior commissure, the posterior group extends transversely fl'om the optic tract laterally to the pretectal region medially, incorporating the dorsal part of the medial geniculate body, the ventral part of the n. lateralis posterior, most of the suprageniculate nucleus and adjacent portions of the pretectum. Ventrally it merges with the principal and magnocellular divisions of the medial geniculate body and, immediately caudal to this level, fades into the principal division., the mesencephalic reticular formation and the deep layers of the superior colliculus. This description is similar to that of Moore and Goldberg 40 who have subdivided the posterior group into two components:

Brain Research, lO (1968) 369 391

CORTICO-THALAMIC CONNEXIONS

37 J

a lateral division which receives ascending fibres from the inferior coUiculus and a medial division which does not. In the course of the present investigation this subdivision has been confirmed and in certain respects extended or~ the basis of corticothalamic connexions. The total thalamic projection

of the

somatic seJlsory cortex

From experiments such as 278 (Fig. 1) in which considerable portions of the first (SI) and second (Sll) somatic sensory areas have been destroyed, the distribution of cortico-thalamic fibres from the somatic sensory cortex as a whole may be defined. In this experiment there is a band of cortical necrosis extending across the som-

I ~'..//,Z//~ol ,--

--

~ ~

z, ~ J

..:---//7,

S../

-,:P\ ,'%m .-'~'x

,J

I

-::

"t .,,',,

Fig. 1. To show the lesion and the extent of the degeneration in the n. ventralis posterior and the posterior group in Experiment 278 in which S1 and SI1 were damaged. In this and subsequent figures, terminal degeneration is indicated by stippling and degenerating fibres of passage by rows of coarse dots. The somewhat indistinct boundaries of the posterior group are shown 0y broken lines and it should be noted that while the supragenicutate nucleus is labelled separately, it forms a part of the medial division (Pom) of the group. See page 388 for abbreviations in this and following figures.

Brain Research, 10 {1968) 369-391

372

Z. G. JONES A N D Y. P. S. P O W E L L

aesthetic areas from the medial end of the ansate s ulcus to a point just above the orbital sulcus. With the exception of a small region in the anterior suprasylvian gyrus, white matter is not involved. Large numbers of degenerating fibres enter the white matter from all parts of the lesion and can be followed through the anterior limb of the internal capsule to the cerebral peduncle. Many of these degenerating fibres leave both the capsule and the peduncle and are distributed to the n. ventralis posterior and to a part of the posterior thalamic nuclear group. Fibres directed to the former nucleus chiefly enter its ventrolateral aspect by passing from the internal capsule through the reticular nucleus; a few entering a little more dorsally, however, reach the nucleus via the internal medullary lamina. Heavy terminal degeneration fills both the lateral (VPL) and medial (VPM) subdivisions of the n. ventralis posterior. The finer axon fragments are densely aggregated around the large cells of the nucleus and give a characteristic reticulated appearance to the neuropil (Fig. 2). Most of the degenerating fibres passing from the damaged cortex to the posterior group leave the cerebral peduncle and reach the posterior group via the zona incerta or, more caudally, the substantia nigra. Terminal degeneration does not fill the whole posterior group but is restricted to a portion of its medial division as defined by Moore and Goldberg 4°. When followed in a rostro-caudal sequence of coronal sections, this degeneration first becomes visible in a restricted area lying dorsomedial to VPM at the level of the habenulo-interpeduncular tract (Fig. 1). It may be followed caudally in this position until VPM is replaced by the medial lemniscus, at which point the degeneration comes to occupy a small zone at first intercalated between the medial lemniscus and the magnocellular division of the medial geniculate body, but later situated dorsomedial to both the lemniscus and the magnocellular division and approaching the ventrolateral margin of the superior colliculus. The remainder of the posterior group, including the suprageniculate nucleus, is free of axon fragments. Degeneration is far less intense in the posterior group when compared with that in the n. ventralis posterior, lacking particularly the dense reticulated feltwork of fine degenerating fibres. Terminal degeneration (Fig. 2) commonly appears as small grape-like clusters in association with dendrites or small cell somata; while some of this degeneration encroaches upon the magnocellular division of the medial geniculate body, terminal ramifications are never visible about the large cells. In this experiment and in all subsequent ones involving lesions in the somatic sensory areas, additional degeneration is present in parts of the reticular nucleus but in no other thalamic nucleus; further degeneration is seen in the zona incerta, substantia nigra, red nucleus and lateral part of the superior colliculus. No degeneration appears in the contralateral thalamus. Projections from SI and SII In another group of experiments, of which 350 is an example (Fig. 3), large lesions were placed to destroy most of SI without damaging adjoining areas. The distribution of terminal degeneration in the thalamus is identical to that described in the previous experiment, again filling both VPM and VPL and extending through the same ventromedially restricted portion of the posterior group. (Slight differences Brain Research, 10 (1968) 369-391

Fig. 2. Photomicrographs showing: (a) degeneration in the n. ventralts posterior o uay~ mt:L a , ~ . . . . . in Sll, × 650; (b) terminal degeneration in the n. ventralis posterior 3 days after a lesion in SI, x 650; (c) terminal degeneration in the posterior group 3 days after a lesion in SI1, :< 650; (d) degeneration in the posterior group 6 days after a lesion in SL :~ 650. Nauta-Gygax stain.

Brain Research, l0 (1968)369-391

374

E. G. JONES AND T. P. S. POWELL

in the distribution of degeneration shown in Figs. l, 3 and 4 are more apparent than real, arising from minor variations in the level and plane of the sections illustrated.) Experiments of this type may be compared with those in which large lesions were restricted to SII. Cat 337 is an example (Fig. 4) in which all but the hindlimb region of SII is damaged. As in the experiments with large S| lesions, degeneration is found in the n. ventralis posterior and in the posterior group. Both VPM and VPL contain termilml degeneration, the overall intensity being, perhaps, slightly less than that seen after lesions in SI. VPM is filled, although the degeneration in its most medial part is sparser than elsewhere; most of VPL also contains degeneration with the exception of its anterolateral corner (Fig. 4), a region which contains the representation of the hindlimb 41. That Sll projects throughout the whole of VPL is established by the presence of degeneration in the anterolateral aspect of the nucleus when, in other experiments, the hindlimb region of SII was damaged. In the posterior group, degeneration occupies the same ventromedially restricted portion described in the

I

THo

i

Fig. 3. To s h o w the extent of the lesion a n d the resulting thalamic degeneration in Experiment 350 in which m o s t o f SI was d a m a g e d .

Brain Research, 10 (1968) 369-391

375

CORTICO-THALAMIC CONNEXIONS CAUDAL

MEDIAL

,

,'~.i i ~ " j L . -A- ' T " E - : R A: L ,

ROSTRAL

r :'.: :'..

M

Fig. 4. To illustrate Experiment 337 in which the lesion (top left) destroyed all but the hindlimb region of SII. The total extent of the degeneration in the n. ventralis posterior is outlined by a heavy line on the orthogonal reconstruction of the nucleus (top right). Note sparing of the anterolateral aspect, containing the representation of the hindlimb. The lines on the orthogonal diagram are at 0.5 mm intervals and the broken line represents the boundary between VPM and VPL. On the sections the degeneration can be seen to affect the same restricted portion of the posterior group as after an SI lesion (Fig. 3).

preceding experiments, although, as it is followed caudally, it becomes a little more extensive dorsally and encroaches upon the stratum griseum profundum of the superior colliculus. As the survival period used in all of the experiments so far described was relatively long (6-7 days), it was necessary to attempt to establish that much of the fine axonal fragmentation seen in the thalamus did not. in fact. represent retrograde degeneration of thalamo-cortical fibres. In five experiments, therefore, a survival period of only 3 days was allowed : in three of these most of SI. and in two most of SII, was destroyed. In each case it was possible to stain fine fragmented pericellular ramifications in both the n. ventralis posterior and the posterior group (Fig. 2). Brain Research, 10 (1968) 369-391

376

E. G. JONES A N D T. P. S. P O W E L L

The appearance of the pericellular degeneration is similar to, though finer than that seen at 6 or 7 days, but far fewer degenerating fibres are visible; in places where the latter do appear they are thin and tend to be irregularly distorted and beaded rather than obviously fragmented. The intensity of the degeneration is appreciably less in both nuclei than after the longer survival period but its distribution is identical. Thus, while at the longer period, retrograde axonal degeneration may be present in one or both sites, its presence does not obscure the pattern of co,:tico-thalamic degeneration. The organhation

o.I"the

projections from SI and SII upon the n. lentra/is poslerior

In this section a group of experiments is described which illustrates the topographical organization of the projections from SI and S If to the n. ventralis posterior. These examples are drawn from a large number of experiments in which small localized lesions were placed in different parts of the somatic sensory areas. In addition to causing degeneration in different parts of the n. ventralis posterior, all lesions have resulted in small amounts of degeneration in the same ventromedially restricted part of the poste:ior group as established above, but it is, in general, too little to be confident of" any degree of topographical organization therein. The first experiments relate to the projection from SI: in Experiment 300 there is a small lesion at the medial end of the posterior sigmoid gyrus affecting mainly the cortex containing the representation

CAUDAL

'S,'

,

S'-:":

,,/i/j l

""

f

,'~

W"7

Fig. 5. To show the lesion in the distal hindlimb region of SI in Experiment 300 and the resulting degeneration in the n. ventralis posterior. The sections are from the levels indicated on the orthogonal reconstruction. Brain Research, 10 (1968) 369-391

377

COR~FICO-THALAMIC CONNEXIONS

CAUDAL /

MEDIAL(

/

'LATERAL

%"'~"'"

ROSTRAL

) 0

//"

Fig. 6. Showing the lesion and the extent of the degeneration in Experiment 279 in which the prox~ma forelimb and adjacent parts of the head and trunk regions of SI were damaged.

CAUDAL .,/

f/

\

(

\ j

I

/

-" ~ LATERAL _

L- I

-S

ROSTRAL

c l i f f - - - J ~ }, \

Fig. 7. To illustrate Experiment 315 in which a small portion of the face region of SI was destroyed.

Brain Research, 10 (1968) 369-39i

378

I7. O. JONES AND T. P. S. POWELL

@

f k

"cAu°A.-------Z,

,/,,- ~l~Z ./LATERAL

DIAL,(- ~ l ~ "

V

ROSTRAL

J,"i), .,.

,i/=/ /

] \ "=Si /l "i

/

/

Fig. 8. Showing the site of the lesion and the extent of the degeneration in the n. ventralis posterior in Experiment 304 in which mainly the limb regions of SI1 were damaged.

of the distal part of the hindlimb (Fig. 5). Degeneration in the n. ventralis posterior is confined to a narrow, curved, peripheral lamella occupying the anterolater:~l aspect of VPL in a region approximately corresponding to the tha!amic representation of the hindlimb 41. In Experiment 279 (Fig. 6) in which the cortical lesion has destroyed the portion of SI spanning the upper end of the coronal sulcus and related to the proximal part of the forelimb and adjacent parts of the head and trunk, degeneration is found in a different part of the n. ventralis posterior. In this case, mainly the middle third of the cross sectional area of VPL is affected, especially in the middle of its rostrocaudal extent; there is also some extension medially into the adjacent dorsal aspect of VPM. Such a distribution would conform approximately to the portions of the nucleus functionally related to the same part of the periphery as those destroyed by the lesion in the cortex. It is difficult to determine whether the degeneration forms a lamella concentric with that seen in the previous experiment but it is significant that the more peripheral portions of VPL are spared. In another experiment (232, Fig. 10) a lesion, placed in the posterior sigmoid gyrus so as to involve mainly the trunk region of SI, caused degeneration in the middle of VPL in a complementary position between, and overlapping> that seen in the previous two but with the axon fragments occupying only the dorsal aspect of the nucleus, in a further experiment (315) a portion of SI related to the lower part of the face in the posterior bank of the coronal sulcus was destroyed by a small stab wound (Fig. 7). In this case, the thalamic degeneration occupies a restricted portion of VPM, mainly in its middle third. Such a position is in keeping with the representation of the appropriate part of the body surface ~l and it could again be interpreted as a lamella, concentric with those seen in the previous three experiments. Brain Research, 10 (1968) 369-391

379

CORTICO-THALAMIC CONNEXIONS

When lesions are placed in different parts of Sll, the distribution of the resulting degeneration in the n. ventralis posterior follows the same pattern found after lesions in SI. It has already been demonstrated in Experiment 337 (Fig. 4) that, in the absence of involvement of the hindlimb region of SII, the anterolateral portion of VPL lacks degeneration. In another experiment (304) in which the lesion primarily involves the forelimb and proximal hindlimb regions of Sii but spares the trunk and greater part of the face representations (Fig. 8), axonal fragmentation extends throughout most oF VPL but affects particularly the forelimb and hindlimb regions, there being somewhat less in its dorsomedial part (trunk region). A few additional fragments extend into the lateral part of VPM. In a further experiment (237), the lesion damages especially the forelimb and trunk regions of Sll, but again, there is probably slight overlap into the face and proximal hindlimb regions (Fig. 9). In this case, there is extensive degeneration in VPL the dorsomedial part now being involved but the anterolateral aspect containing the distal hindlimb representation escapes ', there is, again, extension into adjacent parts of VPM. Results from these experiments are summarized in Fig. 10, and they indicate that only portions of the nucleus containing the representation of the same part of the periphery receives fibres from parts of SI and SII. Thalamic proiections./)'om area 5

The thalamic projections from area 5 will be considered here because there is a suggestion that the anterior portion of the middle suprasylvian gyrus which includes a part of this field, represents a third somatic sensory projection area receiving fibres

CAUDAL

ROSTRAL

/ .!:::.~.::;..\

"x /

/)\""

J

\oL \

/Xb'-F

) Fig. 9. To show the lesion occupying mainly the forelimb region of SII a n d t h e resulting degeneration in the n. ventralis posterior, in Experiment 237. Brain Research, l0 (1968) 369-391

380

1~. G. JONES AND T. P. S. P O W E L L

500

/~

CAUDAL

ROSTRAL

0.~~':'""" '"" / ROSTRAL

Fig. 10. Composite diagrams summarizing theresults of experimentswith small lesions in different parts of SI (A) and SII (B). The lesions have been transferred to a standard diagram of the brain and the extent of the degeneration in the n. ventralis posterior is shown on the orthogonal reconstructions. Note that the degeneration in thenucleus varies according to the subdivision of SI or SII destroyed and in each case can be correlated with the nuclear representation of the body surface.

from VPM13,15. There are a n u m b e r o f experiments with lesions in area 5, particularly in that part occupying the suprasylvian gyrus, but in none o f these has d e g e n e r a t i o n been observed in the n. ventralis posterior. The findings in these brains are, however, o f sufficient relevance to w a r r a n t a description o f one example. In Experiment 334 (Fig. I1), there is an area o f d a m a g e confined to the cortex in the suprasylvian p a r t o f area 5 and d e g e n e r a t i n g fibres can be traced from it t o w a r d s the t h a l a m u s where m a n y o f them, entering its dorsal part, are distributed to the n. lateralis posterior and to the posterior group. Terminal d e g e n e r a t i o n does not fill the n. lateralis posterior but is confined to its rostral two-thirds and, over this extent, mainly affects its ventromedial q u a d r a n t as seen in the coronal sections; the n a r r o w segment of the p o s t e r i o r g r o u p which separates it from VPM is, however, clear. As in the n. lateralis posterior, only a part o f the p o s t e r i o r g r o u p contains terminal d e g e n e r a t i o n : the p o r t i o n involved is far m o r e extensive t h a n that affected after lesions in the somatic sensory cortex. It mainly lies d o r s o m e d i a l to the latter region but there is some overlap adjacent to the m e d i a l lemniscus; for most o f its extent the d e g e n e r a t i o n is coextensive with the Brain Research, 10 (1968) 369-391

CORTICO-THALAMICCONNEXIONS

38t

,cM"N

Fig. 11. To illustrate Experiment 334in which a part of area 5 was damaged. Note that thethalamic degeneration occupies a localized portion of the n. lateralis posterior and a part of the posterior group which is largely coextensive with the suprageniculate nucleus.

suprageniculate nucleus, although at the level of the posterior commissure it expands laterally somewhat to come into relation with the brachium of the superior cotliculus. When followed rostrally the degeneration in the posterior group shades insensibly into that in the n. lateralis posterior and, similarly, the more caudally situated degeneration merges with that in the deep layers of the superior colliculus. As in the case of area 5 lesions, a series of experiments involving lesions in the motor, premotor, visual, auditory and other parts of the suprasylvian cortex did not result in degeneration in the n. ventralis posterior. Small lesions in the motor cortex suggest some degree of organization in its projection to the n. ventralis lateralis and further degeneration appears in the centre median-parafascicular complex.

Further consideration of the posterior group The portions of the posterior group showing degeneration after somatic sensory

Brain Research. 10 (1968) 369-391

382

E. G. JONES AND T. P. S. POWELL

and area 5 lesions, together, comprise a good deal of the medial division of the group as defined by Moore and Goldberg 4°. To further confirm that SI and Sll project upon essentially the same portion of the medial division, two experiments will be described in which the brains were cut in the horizontal plane as the two divisions are, in general, more readily distinguishable in this plane of section (Fig. 12). In Experiment 236, the lesion is in SI and has destroyed most of the posterior sigmoid and upper part of the coronal gyri, while that in Experiment 264 is in SI1, on the summit of the anterior ectosylvian gyrus. In each of these experiments there is degeneration in the posterior group and in the horizontal sections of Fig. 12, which are at approximately the same level, it can be seen to occupy in each case a small region between the caudal pole of the n. ventralis posterior and the magnocellular division of the medial geniculate body,

C

"':':i"-"X~i ::: ':: "

"

r,,

9

x,

E---

-

@_ ', .t"~-'. :~:'~4~:h:

Fig. 12. To show the degeneration in the posterior group in a series of experiments inwhich the brains were sectioned horizontally. In A and B, inwhich experiments with lesions in Sl (A) and Sll (B) are illustrated, the degeneration isconfinedto the same part of the medial division of the posterior group. When the auditorycortexisdestroyed (C) the degeneration is restricted to the lateral division. The sections are from the levels indicated. Anterior is to the left.

Brain Research, 10 (1968) 369-391

CORTICO-THALAMIC CONNEXIONS

383

and extending somewhat rostrally along the medial aspect of VPM. In contrast to this, when a lesion involves the auditory cortex as in Experiment 270 (Fig. 12), this medial part of the posterior group is unaffected but terminal degeneration. instead, fills a somewhat complementary lateral component of the group lying in the region bounded by the auditory radiations and the magnocellular division of the medial geniculate body, and extending rostrally along the lateral aspect of the n. ventratis posterior. This region conforms closely to the lateral division of the posterior group 40 and has been shown to receive ascending fibres from the inferior colliculus '~0. DISCUSSION

This study has shown that the cortical areas SI and SII each projects in a topographically organized manner upon the n. ventratis posterior and in addition each projects upon the same part of the posterior group ot' thatamic nuclei; the several implications of this statement will be discussed separately, A number of recent papers have drawn attention to the fact that in any study of cortico-thalamic connexions with techniques for axonal degeneration, it is essential to take into account that even at such relatively short survival periods as 8 days, the interpretation of the degenerative changes is complicated by the presence of silver stained fragments which may represent retrograde degeneration of thalamo-cortical fibres12, 21,4~. As 7--10 days is the survival period most commonly used with the Nauta technique, it is impossible to be certain that, at this stage, all the degeneration seen in a n y thalamic nucleus is not of a retrograde nature; and therefore, such techniques cannot demonstrate the presence of cortico-thalamic fibres with complete certainty, in an attempt to circumvent this difficulty, parallel experiments have been performed in which animals with identical lesions in SI or SII were permitted to survive for 3 and 7 days, as it was felt that at the shorter survival time retrograde changes would be absent or minimal. After 3 days it was possible to stain, in both the n. ventralis posterior and in the posterior group, very fine, fragmented, pericellular ramifications which most probably represent genuine orthograde degeneration of cortico-thalamic axons. As the distribution of the degeneration at 3 days was identical to that seen following similar lesions at 7 days. it seemed reasonable to use the longer survival period for, while the degeneration observed in each experiment may be a mixture of both orthograde and retrograde axonal break-up, the staining procedure presents fewer difficulties. The existence of cortico-thalamic fibres in the cat is confirmed by the electron microscopic demonstration of degenerating terminals in the n. ventralis posterior and in the medial and lateral geniculate bodies following lesions in the appropriate cortical area 27,2~,'~3 (Fig. 13). One of the significant features of the present observations seems to be that the projection of the n. ventralis posterior upon the somatic sensory cortex is reciprocated by returning cortico-thalamic fibres. The influence exerted by fibres of cortical origin upon transmission in the spinal cord and dorsal column and trigeminal nuclei is now well established z,6,14,z°,2z,S4 and cortico-thalamic fibres might be expected to mediate similar effects upon the thalamic relay nuclei. That this is so for the n. ventralis posterior Brain Research, 10 (1968) 369-391

384

E. G. JONES AND T. P. S. POWELL

Fig. 13. Electron micrographs demonstrating degenerating axo-dendritic (a) and axo-axonic (b) terminals (DT) in the n. ventralis posterior 4 days after a lesion involving S! and SII. Fixatien by glutaraldehyde and formaldehyde; double stained with lead citrate and uranyl acetate; G, glycogen.

is indicated by the work of Andersen et al. ~ who showed that a train of corticothalamic impulses descending from SI will depolarize the relay cells and facilitate the transmission of orthodromic volleys at medium and high frequencies. The demonstration of axo-axonic as well as axo-dendritic terminations of cortico-thalamic fibres within the n. ventralis posterioreT, ')s (Fig. 13) suggests that the synaptic organization of the nucleus is a complex one and before all the events taking place in the nucleus can be analysed, a detailed electron microscopic study of the mode termination of all its afferent pathways will be necessary; similarly, the role of interneurons 4 will have to be further investigated. It has now been established by both physiological ')3 and anatomical27, 37 methods that different parts of the n. ventralis posterior project discretely upon functionally related parts of both SI and Sll so it is not surprising that each of these cortical areas sends fibres back to the nucleus. The present study indicates that both Si and SII project throughout the whole of VPM and VPL, confirminga brief comment by Mehler 3s. This is probably to be expected as SI and Sil each contain complete representations of the bodysurface 58, but in regard to the projection of Sll it stands in contrast to the findings of De Vito 16 who emphasises the paucity of degeneration in rostral parts of VPL following lesions in that cortical area. Because two separate Brain Research, 10 (1968) 369-391

CORTICO-THALAMIC CONNEXIONS

385

cortical areas send fibres to the n. ventralis posterior it is probable that the nucleus receives two different sorts of descending influence, but so few functional differences have been demonstrated between SI and SII that one can only speculate regarding the differential nature of such influences. As there is now evidence2, v that single neurons in the n. ventralis posterior send axon branches to both SI and Sll, it would be interesting to determine whether fibres returning from these areas end on the same or different cells. It would, similarly, be of value to determine whether fibres from the two areas terminate on the same or different parts of the neurons in the nucleus as this might indicate the degree of functional similarity or otherwise. From the experiments with small lesions in SI or SI1, a topographical organization has been demonstrated so that only parts of S1 and SII receiving fibres from a given part of the n. ventralis posterior send fibres back to it. In all cases it has been possible to relate with a fair degree of accuracy, the distribution of degeneration to the representation of the body surface in the nucleus, and it conforms approximately to the concentric, lamellar pattern described by Mountcastle and Henneman 41. To demonstrate the foregoing conclusively would necessitate using very small lesions confined to one or two dermatomal regions of the cortex, but the present experiments at least support the observation that the trunk is represented only dorsally while the apical limb regions extend throughout the whole dorsoventral extent of the nucleus (cfi Experiments 232 and 300). As a result of this highly organized topographic pattern, portions of the nucleus containing the representation of the head, trunk and proximal segments of the limbs must be subjected to a somewhat different cortical influence from that affecting parts representing the distal segments of the limbs: in both SI and SII, cortex related to parts of the body lying close to the midline is joined to symmetrical regions of the opposite hemisphere by commissural fibres whereas the distal limb regions lack such interhemispheric connexions~7,'~7, '~9. Thus, corticothalamic influences descending from the distal limb regions must be relatively 'purer' for not having been subjected to interhemispheric integration. The question has previously been raised "9 as to whether this relative 'purity' could play a part in rendering the distal portions of the limbs more sensitive in somaesthetic discrimination, perhaps by affecting the size of the peripheral field or the amount of inhibitory surround exhibited by neurons in the thalamus. While a certain amount of evidence is accruing to suggest that the several ascending afferent pathways converging upon the n. ventralis posterior terminate in slightly different parts of the nucteus 34-z6, the present findings indicate that the cortico-thalamic fibres are distributed simply according to the representation of the body surface described by Mountcastle and I-lenneman 41. It has been suggestedZ% on the basis of their cortical association and commissural connexions, that the two known cortical projection areas of Group 1 muscle afferents 7,45 should be considered as parts of SI and SIt intimately related to the distal forepaw region of each area; from the pattern of organization of the cortico-thalamic fibres they would each project back to VPL in the region of the distal forepaw representation - - and this is approximately the position indicated by Andersson e t al. 7 as the Group 1 afferent relay in the thalamus. Brain Research, 10 (1968) 369-391

386

E. G. JONES AND T. P. S. POWELL

It has been difficult to place lesions selectively in the several architectonic areas which comprise the somatic sensory cortex as the individual fields are very narrow in the cat ~4. It may be noted, however, that in Experiments 300 and 315, the lesions mainly affected area 3 while that in Experiment 279 mainly occupied area 2. Each of these caused degeneration in a restricted part of the n. ventralis posterior but it could be interpreted best in terms of the representation pattern in the nucleus. No fibres were observed passing from cortical areas outside SI and SII to the n. ventralis posterior and, conversely (apart from the reticular nucleus which receives fibres from the whole cortex l°) SI and SII do not project to thalamic nuclei other than the n. ventra[is posterior and the posterior group. On the basis of his findings on stimulation in VPM, Darian-Smith has adduced evidence that a certain proportion of its cells has discrete axon projections to a 'third somatic sensory projection area' at the anterior end of the middle suprasylvian gyrus13,15, a region which has been equated with the architectural field, area 5 (refs. 27, 30). Lesions in VPM do not cause degeneration in area 5 (ref. 27), and the present results show that this area does not project to VPM. It does, however, project heavily upon the n. lateralis posterior and upon a considerable portion of the posterior group. Each of these nuclei lies in close proximity to VPM and, especially caudally where most of Darian-Smith's penetrations were made, the boundaries between all three are far from distinct. It seems possible, therefore, that the 'third somatic sensory area' may be receiving its input from regions adjacent to VPM rather than from VPM itself. In demonstrating a projection from SIi to the posterior group of thalamic nuclei, the present results confirm those of Mehler 3s and De Vito 16 but, as also noted by Mehler, it is a striking fact that SI also projects to the same part of the group. Thus, while much past work has been concerned with the relationship of the posterior group to SII and to the auditory cortex47, 51, there is now less reason for considering it to be exclusively related to these areas. This is further strengthened by the demonstration that area 5 also projects to it. The portion of the posterior group with which SI and SII are connected is identical to that shown by Mehler 3s to receive fibres bilaterally from the spinal cord, but it isconsiderablyless extensive than the total posterior group defined by other workers 4°,47,s°,'5~ and constitutes only the rostral and ventral part of Moore and Goldberg's medial division 4°. It may be noted that the auditory cortex also projects only to that part of the posterior group which receives fibres from the ascending auditory pathway (the lateral division40). These findings would suggest that there may be some degree of functional parcellation within the posterior group and, therefore, that it may not be quite so heterogeneous a region as suggested by Poggio and Mountcastle 47 who considered the properties of the region as a whole rather than as a sum of individual parts. It may, however, be an oversimplification to consider that the different elements of the posterior group are entirely separate functionally for, while in Poggio and Mountcastle's study some neurons responded to sound or light touch only, many others were not modality specific and could be activated by a wide variety of stimuli including light mechanical, auditory, vibratory and others which were destructive of tissue; most cells responding to cutaneous stimuli could, moreover, be activated from very large, often bilateral, receptive fields (see also Brain Research, l0 (1968) 369-391

CORTICO-THALAMIC CONNEXIONS

387

Whitlock and PerlST). Such findings would indicate some overlap and convergence. The bilateral input to the posterior group shown by physiological methods has been confirmed anatomically 3s and might be advanced as a possible basis for the bilateral representation of the body surface in Sll, although certain difficulties such as the high proportion of cells with 'lemniscal' properties 11 would need to be resolved. The restricted part of the posterior group which receives fibres from SI and SII has been said to project back only to SI1 (ref. 38), a finding which could support the above proposal. It does, however, seem unlikely on purely a priori grounds that S1, which like SII sends fibres to the posterior group, should stand alone in not receiving fibres back from it, and a final decision must await a more comprehensive study of the efferent connexions of the posterior group. Following this and other studies, it now seems apparent that, in the somatic sensory system at least, the sensory cortical areas project subcortically to most of the sites to which their ascending pathways distribute fibres. Thus, corticofugal fibres pass to the n. ventralis posterior and posterior group of the thalamus, to the superior colliculus 19, to the dorsal column and trigeminat nuclei sa,sa and to the spinal cord4~: even the zona incerta may be included for it, too, appears to receive ascending fibres in the opossum is and rat3S, a6. It has been suggested 19,'e that the fine fibres passing from the visual cortex to the lateral geniculate nucleus may be collaterals of larger fibres passing to the n. lateralis posterior or to the superior colliculus, and if this suggestion is substantiated it will raise the question as to whether many or all of the subcortical connexions of a sensory area are effected by collaterals of single fibres. From the point of view of thalamo-corticat relations, however, perhaps a more significant conclusion is that every sensory cortical area is now known to send fibres to its relevant relay nucleus together with at least one other - - the n. ventralis posterior and the posterior group in the case of the somatic sensory, the principal division o f the medial geniculate nucleus and the posterior group in the case of the auditory, and the lateral geniculate nucleus and the n. lateralis posterior in the case of the visuap,9,1,~. Moreover, it seems likely that this generalization may be extended to all cortical areas, for the motor and premotor areas project to their relevant main nucleus and to the intralaminar nuclei s,ag,L~3, while area 5 sends fibres to the n. lateralis posterior and to the posterior group. Whether in each case one of these connexions is effected by collaterals of axons passing to the other site remains to be ascertained but, if so, it could in a sense represent an interesting inversion of the concept of Rose and Woolsey r'~ that certain thalamic nuclei may send essential projections to one cortical area and sustaining projections to others, as one possible interpretation of their observations is that a sustaining projection is a collateral oneaL In the absence of detailed information regarding the further connexions of the posterior group, it is difficult to assign a functional role to this double set of connexions. It is interesting to speculate, however, as to whether efferent fibres from the posterior group pass back only to those cortical areas from which it receives fibres, thereby constituting a simple feedback loop, or whether they pass to other - - perhaps functionally more complex - - cortical areas, in which case they could represent a route for further elaboration of sensory information. Brain Research, 10 (1968)369-391

388

E. G. JONES AND T. P. S. POWELL

ABBREVIATIONS USED IN FIGURES BCI BCS CL CM CP CS GL GMm

-- brachium of the inferior colliculus -- brachium of the superior colliculus nucleus centralis lateralis -- nucleus centrum medianum -- posterior commissure = superior colliculus -- lateral geniculate nucleus - medial geniculate nucleus pars magnocellularis GMp medial geniculate nucleus pars principalis LD nucleus lateralis dorsalis LM -: medial lemniscus LP -- nucleus lateralis posterior M D -- nucleus medialis dorsalis NR = red nucleus P =: pulvinar Ped -: cerebral peduncle

Pf Pol

nucleus parafascicularis lateral division of the posterior thalamic nuclear group Pore medial division of the posterior thalamic nuclear group Pt pretectal area R -- thalamic reticular nucleus SG nucleussuprageniculatus SN substantia nigra TH habenulo-pedunculartract TO optic tract VA nucleus ventralis anterior VL nucleus ventralis lateralis VP nucleus ventralis posterior VPL nucleus ventralis posterolateralis VPM nucleus ventralis posteromedialis ZI zona incerta III oculomotor nerve

SUMMARY The cortico-thalamic connexions of the somatic sensory and certain related areas of the cerebral cortex have been studied in the cat using the N a u t a technique. Both the first (Sl) and second (SII) somatic sensory areas send fibres to the ipsilateral n. ventralis posterior in a topographically organized m a n n e r which conforms closely to the concentric lamellar representation of the body surface in the nucleus. Both SI and SII also send fibres to the same part of the medial division of the ipsilateral posterior thalamic nuclear group. This ventromedially restricted portion of the group is the same as that which receives fibres bilaterally from the spinal cord. Area 5 sends fibres to the n. lateralis posterior and to a p o r t i o n of the medial division of the posterior group consisting mainly of the suprageniculate nucleus, while the auditory cortex projects to the medial geniculate nucleus and to the lateral division of the posterior group. F r o m these results and those of studies on other cortical areas it would appear that every cortical area sends efferent fibres to its main thalamic nucleus together with one other. ACKNOWLEDGEMENT This work was assisted by a grant from the Medical Research Council and was carried out d u r i n g the tenure by E.G.J. of a Nuffield D o m i n i o n s D e m o n s t r a t o r ship, on leave from the University of Otago, New Zealand.

REFERENCES 1 ALTMAN, J., Some fiber connections to the superior colliculus in the cat, J. comp. Neurol., 119 (•962) 77-96. 2 ANDERSEN,P., ANDERSSON,S. A., ANO LANOGREN,S., Some properties of the tbalamic relay cells in the spino-cervico-lemniscal path, Acta physiol, scand., 68 (1966) 72-83. Brain Research, 10 (1968) 369-391

CORTICO-THALAMIC CONNEX1ONS

389

3 ANDERSEN, P., ECCLES, J. C., AND SEARS, W. A., Cortically evoked depolarization of primary afferent fibers in the spinal cord, J. Neuroflhysiol., 27 (1964) 63-77. 4 ANDERSEN, P., ECCLES, J. C., AND SEARS, T. A., The ventro-basal complex of the thalamus: types of cells, their responses and their functional organization, J. Physiol. (Lond.), 174 (1964) 370-399. 5 ANDERSEN,P., JUNGE,K., AND SVEEN, O., Cortico-thalamic facilitation of sornatosensory impulses, Nature (Lond.), 214 (1967) 101 l - l 012. 6 ANDERSEN, P., ECCLES, J. C., SCHMIDT, R. F., AND YOKOTA, T., Depolarization of presynaptic fibers in the cuneate nucleus, J. Neurophysiol., 27 (1964) 92-106. 7 ANDERSSON, S. A., LANDGREN, S., AND WOLSK, D., The thalamic relay and cortical projection of G r o u p I muscle afferents from the forelimb of the cat, J. Ph.vsiol. (Lond.), 183 (1966) 576-591. 8 AVER, J., Terminal degeneration in the diencephalon after ablation of frontal cortex in the cat, J. Anat. (Lond.) 90 (1956) 30--41. 9 BERESFORD,W. A., Fiber degeneration following lesions of the visual cortex of the cat. In R. JUN(~ AND H. KORN}tUBER (Eds.), Neurophysiologie und Psychophysik des Visuellen Systems, Springer, Berlin, 1961, p. 247. 10 CARMAN, J. B., COWAN, W. M., AND POWELL, T. P. S., Cortical connexions of the thalamic reticular nucleus, J. Anat. (Lond.), 26 (1964) 587-598. 11 CARRERAS, M., AND ANDERSSON, S. A., Functional properties of neurons of the anterior ectosylvian gyrus of the cat, J. Neurophysiol., 26 (1963) 100-126. 12 CRAGG, B. G., Centrifugal fibres to the retina and olfactory bulb, and composition of the supraoptic commissures in the rabbit, Exp. Neurol., 5 (1962) 496-427. 13 DARIAN-SMITH, I., Cortical projections of thalamic neurones excited by mechanical stimulation of the face of the cat, J. Physiol. (Lond.), 171 (1964) 339-360. 14 DARIAN-SMITH, l., AND YOKOTA, T., Corticofugal effects on different neuron types within the cat's brain stem activated by tactile stimulation of the face, J. Neurophysiol., 29 (1966) 185-206. 15 DARIAN-SMITH, 1., ISBISTER, J., MOK, H., AND YOKOTA, T., Somatosensory cortical projection areas excited by tactile stimulation of the cat: a triple representation, J. Physiol. (Lond.), 182 (1966) 671 689. 16 DE VITO, J. L., Thalamic projection of the anterior ectosylvian gyrus (somatic area II) in the cat. J. comp. Neurol., 131 (1967) 67--78. 17 EBNER, F. F., AND MYERS, R. E., Distribution of corpus callosum and anterior commissure in thc cat and raccoon, J. comp. Neurol., 124 (1965) 353-363. 18 ERICKSON, R. P., JANE, J. A., WAITE, R., AND DIAMOND, I. T., Single neuron investigation of sensory thalamus of the opossum, J. Neurophyshd., 27 (1964) 1026-1047. 19 GAREY, L. J., JONES, E. G., AND POWELL, T. P. S., Interrelationships of striate and extrastriate cortex with the primary relay sites of the visual pathway, J. Neurol. Neurosurg. Psych&t, 3l (1968) 135-157. 20 GORDON, G., AND JUKES, M. G. M., Descending influences on the exteroceptive organization of the cat's gracile nucleus, J. Physiol. (Lond.), 291 (1964) 291-319. 21 GUILLERV, R. W., Afferent fibres to the dorso-medial thalamic nucleus in the cat, J. Anat. (Lond.), 93 (1959)403 419. 22 GUILLER¥, R. W., Patterns of the fiber degeneration in the dorsal lateral geniculate nucleus of the cat following lesions in visual cortex, J. comp. Neurol., 130 (1967) 197-222. 23 GUILLERY, R. W., ADRIAN, H. O., WOOLSEY, C. N., AND ROSE, J, E., Activation of somatosensory areas l and II of cat's cerebral cortex by focal stimulation of the ventrobasat complex. In D. P. PURPURA AND M. D. YAHR (Eds.), The Thalamus, Columbia Univ. Press, New York, 1966, p. 197. 24 HASSLER, R., UND MUHS-CLEMENT, K., Architektonischer Aufbau des sensomotorischen und parietalen Cortex der Katze, J. Hirnforsch., 6 (1964) 377-420. 25 JABBUR, S. J., AND TOWE, A. L., Cortical excitation of neurons in dorsal column nuclei of cat, including analysis of pathways, J. Neurophysiol., 24 (1961) 499-509. 26 JASPER, H. H., AND AJMONE MARSAN, C. A., A Stereotaxic Atlas of the Diencephalon of the Cat, National Research Council of Canada, Ottawa, 1954. 27 JONES, E. G., Pattern of cortical and thalamic connexions of the somatic sensory cortex, Nature (Lond.), 216 (1967) 704-705. 28 JONES, E. G., Interrelationships of the somatic sensory cortex and thalamus in the cat, J. Anat. (Lond.), in press. 29 JONES, E. G., AND POWELL, T. P. S., The commissural connexions of the somatic sensory cortex in the cat, J. Anat. (Lond.), in press. Brain Research, l0 (1968) 369-391

390

E. G. JONES AND T. P. S. POWELL

30 JONES, E. G., AND POWELL, T. P. S., The ipsilateralcortical connexions of the s~m3atic sensory areas in the cat, Brain Research, 9 (1968) 71-94. 31 KRIEG, W. J. S., Connections o f the Cerebral Cortex, Brain Books, Evanston, I!1., 1963, 237 pp. 32 KUSAMA,T., OTANI, K., AND KAWANA, E., Projections of the motor, somatic sensory, auditory and visual cortices in cats. In Y. TOKIZANE AND J. P. SCHAD~ (Eds.), Progress #1 Brain Research, Vol. 21, Correlative Neurosciences, Part A : Fundamental Mechanisms, Elsevier, Amsterdam, [ 966, p. 292. 33 KUYPERS, H. G. J. M., An anatomical analysis of cortico-bulbar connexions to the puns and lower brain stem in the cat, J. Anat. (Lond.), 92 (1958) 198 218. 34 LANDGREN, S., NORDWALL, A., AND WENGSTROM, C., The location of the thalamic relay in the spino-cervico-lemnisca[ path, A eta physiol, scand., 65 (1965) 164 175. 35 LUND, R. D., AND WEBSTER, K. E., Thalamic afferents from the dorsal column nuclei. An experimental anatomical study in the rat, J. comp. Neurol., 130 (1967) 301-312. 36 LUND, R.. D., AND WEBSTER, K. E., Thalamic afferents from the spinal cord and trigeminal nuclei. An experimental study in the rat, J. cutup. Neurol., 130 (1967) 313 328. 37 MACCm, G., ANGELERI, E., AND GUAZZI, G., Thalamo-cortical connections of the first and second somatic sensory areas in the cat, J. cutup. Neurol., l I I (1959) 387-405. 38 MEHLER, W. R., Some observations on secondary ascending afferent systems in the central nervous system. In R. S. KNIGHTON AND P. R. DUMKE (Eds.), Pain, Churchill, London, 1966, p. I 1. 39 MEHEER, W. R., Further notes on the center median nucleus of Luys. In D. P. PURPURA AND M. D. YAHR (Eds.), The Thalamus, Columbia Univ. Press, New York, 1966, p. 109. 40 MOORE, R. Y., AND GOLDBER(~, J. M., Ascending projections of the inferior colliculus in the cat, J. camp. Neurol., 121 (1963) 109-135. 41 MOUNTCASTLE, V. B., AND HENNEMAN, E., Pattern of tactile representation in thalamus of cat, J. Neurophysiol., 12 (1949) 85-100. 42 NAUTA, W. J. H., AND GY~AX, P. A., Silver impregnation of degenerating axons in the central nervous system: a modified technic, Stain Technol., 29 (1954) 91 93. 43 NHMI, K., Klsm, S., MtKI, M., AND FUJ|TA, S., An experimental study of the course and termination of the projection fibers from cortical areas 4 and 6 in the cat, Folia psychiat, neurol, jap., 17(1963) 167-216. 44 NYBERG-HANSEN, R., AND BRODAL, A., Sites of termination of corticospinal fibers in the cat. An experimental study with silver impregnation methods, J. cutup. Neurol., 120 (1963) 369-391. 45 OSCARSSON, O., AND ROSEN, I., Short latency projections to the cat's cerebral cortex from skin and muscle afferents in the contralateral forelimb, J. Physiol. (Lond,), 182 (1966) 164-184. 46 PEELE, T. L., Cytoarchitecture of individual parietal areas in the monkey (Macaca mulatta) and the distribution of the efferent fibers, J. comp. Neurol., 77 (1942) 693-737. 47 POG610, G. F., AND MOUNTCASTLE, V. B., A study of the functional contributions of the lemniscal and spinothalamic systems to somatic sensibility. Central nervous mechanisms in pain, Bull. Johns Hopk. Hosp,, 106 (1960) 266-316. 48 POWELL, T. P. S., AND COWAN, W. M., A note on retrograde fibre degeneration, J. Anat. (Lurid.), 98 (1964) 579-585. 49 RAM6N V CAJAL, S., Histologie du Syst~me Nerveux de I'Homme et des VertObrds, Vol. 11, Maloine, Paris, 1909 1911, p. 398. 50 Rose, J. E., The thalamus of the sheep: cellular and fibrous structure and comparison with pig, rabbit and cat, J. comp. Neurol., 77 (1942) 469-523. 51 Rose, J. E., AND WOOLSEY, C. N., Cortical connections and functional organization of the thalamic auditory system of the cat. In H. F. HARLOW ANt) C. N. WOOLSEY (Eds.), Bioloeical and Biochemical Bases o f Behavior, Univ. Wisconsin Press, Madison, Wise., 1958, p. 127. 52 SCHEmEL, M. E., AND SC~EmEL, A. B., Patterns of organization in specific and nonspecific thalamic fields. In D. P. PURPURA AND M. D. YAHR (Eds.), The Thalamus, Columbia Univ. Press, New York, 1966, p. 13. 53 SZENTAGOTHAI,J., H.~MORI, J., AND T6MBOL, T., Degeneration and electron microscope analysis of the synaptic glomerulus in the lateral geniculate body, Exp. Brahl Res., 2 (1966) 283 301. 54 TOWE, A. L., AND JABBCn, S. J., Cortical inhibition of neurons in dorsal column nuclei of cat, J. Neurophysiol., 24 (1961) 488-498. 55 WALBER~, F., Corticofugal fibres to the nuclei of the dorsal columns. An experimental study in the cat, Brain, 80 (1957) 273-287. 56 WALKER, A. E., The Primate Thalamus, Univ. Chicago Press, Chicago, II1., 1938, p. 249. Bra#l Research, lO (1968) 369 391

CORTICO-THALAMIC CONNEXIONS

391

57 WHITLOCK,D. G., AND PERL, E. R., Afferent projections through ventrolateral funiculi to thalamus of cat, J. Neurophysiol., 22 (1959) 133-148. 58 WOOLSEY, C. N.,Organization of somatic sensory and motor areas of the cerebral cortex. In H. F. HARLOW ANDC. N. WOC)LSEY(Eds.), Biological and Biochemical Bases ol'Behavior, Univ. Wisconsin Press, Madison, Wisc., 1958, p. 63.

Brain Research, 10 (1968) 369-39l