- Email: [email protected]
Glia and the elimination of transient cortical projections
225
TINS - JuIy 1984 Reading list Clarke, J. D. W., Hayes, B. P., Hunt, S. P. and Roberts, A. (1984) J. PhysioL (London) 348, 51 l-525 Freud, S. (1877) Sber. Akad Wiss Wien 75, 15-27 Rohon, V. (1885) Sber. Bayer Akaa! Wiss. Math 14, 39-51 Beard, J. (1889) Proc R Sot (London) 46, 108-118 Lamborghini, J. E. (1980) J Camp. NeuroL 189,323-333 Coghill, G. E. (1914) J Camp. NeuroL 24, 161-234 Hughes, A (1957) J; Anat 91, 323-338 Roberts, A and Hayes, B. P. (1977) Proc R Sot London Ser. B 196,415-429 Roberts, k and Clarke, J. D. W. (1982) Phil
10 11 12 13 14 15 16 17 18
Trans. R Sot London Se,: B 296, 195212 Kahn, J. k and Roberts, A. (1982) Philos. Trans R Sot London Ser. B 296,229-243 Roberts, A and Smyth, D. (1974) J Camp. . PhysioL 88, 3142 Kahn, J. A and Roberts, A (1982) 1 Exp. BioL 99, 185-196 Roberta, A and Stirling, C. A (197 1) Z. VgL PhysioL 71,295-310 Jacobson, M. (198 1) J; Neurosci 1,9 18-922 Jacobson, M (1981) .X Neurosci 1, 923-927 Harrison, R G. (1910) J. Exp. Biol 9, 787848 Roberts, A and Taylor, J. S. H (1982) J EmbryoL Exp. MolphoL 69,231-250 Taylor, J. S. H. and Roberts, A (1983) 1 EmbryoL Exp, MorphoL 75,49-66
Glia and the elimination of trahsient cortical projections Over thepast decade a number ofstudies have demonstrated that during the course of development, corticalprojection neurons undergo major changes in their areai distribution In particular, the distribution of neuronsprojecting to agiven target is much wider in the infant than in the adult This wasfirst demonstratedfor callosal projection neurons in the visual system of the cat’, but since then the observation has beeriextended to callosalprojections of the somatosensory system of the cap, rat’ and monkeyi There is also evidence that similar changes occur in the distribution Of cortical neurons which project sub-cortically 5-7. Other evidence obtained utilizing retrograde double labelling techniques, has suggested that these changes are accomplished not by the elimination of neurons (‘cell deathy0,9 but by the selective elimination of neuronal prqcesses’4 These findings, which were treated in detail in a recent review in TINS by Stanfield”, raise the intriguing question of how axonalprocesses are selectively eliminated dun’ng the course of development.
.
Recently, Innocenti and coworkers pro- their existence coincides with the time vided evidence that a specific type of glial period during which callosal axonal pr@ cell plays a role in the selective elimination cesses are eliminated Third, Innocenti of cortical projections’2,L3. They refer to and collaborators present electron microthis transient cell type as a gitter cell, a graphic evidence of gitter cells surrounding term which, according to Russell, was and presumably engulfing axonal pre introduced by Nissl in 1904 to describe cesses, and of gitter cell vacuoles that phagocytes14. Innocenti et al! chose this contain degenerative debris. In this regard, term for the cell they described in the the gitter cells have been demonstrated by occipital cortex of the cat because it is others to have a number of the characterrelatively free from pre-existing corm* istics of macrophages (see below). Pertations - the literature on CNS phage haps the strongest, although still somecytes is bewildering in its complexity and what indirect, evidence of gitter cell use of synonymsU. The intriguing properinvolvement in axonal elimination, is the ties of the gitter cell, with respect to demonstration by Innocenti and coaxonal elimination, are as follows. First, workers that the clusters of these cells they are found in clusters in the cortical accumulate horseradish peroxidase followwhite matter in regions through which ing injection of this substance into the transient callosal axons must normally opposite hemisphere. Presumably the err travel One cluster in particular, the dorse zyme is not acquired directly by transport medial, is situated in such a position that through gitter cell processes, but is secon& trtisitory axons pass through it on the ary to the phagocytosis of eliminated and way to and from the medial portion of degenerating HRI-labelled callosal axons primary visual cortex (an area which by gitter cells. However, this remains to loses callosal projection neurons)...Second, be directly demonstrated the existence of the gitter cell clusters is The observations and interpretation? of short lived In the cat, they are found only Innocenti and his coworkers are strongly during the first postnatal month Thus, supported by similar observations on the
19 Bixby, J. L. and Spitzer, N. C. (1984) Dev. BioL (in press) 20 Lamborghini, J. E., Revenaugh, M and Spitzer, N. C. 11979) .I Coma. NeuroL 183.741-152 21 Spitzer, N. C. (1983) &DevelopingandRegenersting Vertebrate Nervous Systems (Coates, P. W., Markwald, R R and Kenny, A D., eds), pp. 41-59, Alan R Liss, Inc., New York 22 Blair, L A C. (1983) J. Neurosci 3, 143O1436 23 O’Dowd, D. K. (1983) Nature (London) 303, 619-621 24 Katz, M J. and Lasek, R J. (I 979) J Comp. NeuroL 183, 811-832 25 Lamborghini, J. E. (198 1) Sot Neurosci Abstr 7,291 NICHOWS C. SPITZER Department of Biology, Universiv of California, San Diego, La Jolla, CA 92093, USA .
I
gliai cells in developing rat’s neocortex. Ling described clusters of what he called ameboid microglia in the region of the corpus callosum of the neonatal rat as well as electron micrographs of these cells engulfing unmyelinated axonal process&. In another report”, Ling provided evidence that these cells had some of the histochemical properties of active phagocytes; specifically, they possess high levels of the hydrolytic enzymes acid phosphotase and aryl sulphatase. Ivy andKiIIackey provided evidence that there is a transient population of glial cells in the telencephalon of the neonatal rat which are capable of accumulating horseradish peroxidase18. The location of at least one of these JXRPlabelled glial populations is the same as that studied by Ling and it is in such a position that most callosal axons must pass through it*. Valentino and Jones have confirmed the observations of Ling and provided additional evidence that ameboid micre glia or gitter cells are macrophages by demonstrating that these cells reacted positively to an esterase stain specific to blood monocytes and macrophages and we= also labelled with a monoclonal antibody to macrophage cel&rface polypeptideslg. Another similarity between the gitter cells of the rat and the cat is their transiency. F the rat, clusters of nonneuronal cells, which can be labelled with HRP, are not detectable at the end of the second postnatal week, the time by which *In retrospeq Ivy arid I misinterpreted the HRPlabelling in these glial cells. We assumed that the accumulation of HRP in these cells was the direct result of transport by long glial processes rather than an indirect phenomenon (transport by callosal axon processes which are then engulfed by the gitter cells) as would now seem to be most likely. Thus, it was suggested by Ivy and I that these transient gli& cells may play a role in axonal guidance. However, both the present hypothesis, as well as more recent clear electron microscopic and immunocytochemical evidence that this s&e population pf cells are macrophages make that suggestion very unlikely.
@ 1984. Elrevirr
Science Publishas
RV.. Amsted~
0378 - SPI2/84/S2M)
TINS - July 1984
226
which are degenerating because they have failed to make connections. Undoubtedly, over the next couple of years, there will be much research aimed at answering this question.
the adult distribution of callosal projection neurons is achieved.Finally, it should be pointed out that a similar cell type has been described in the neonatal rat’s spinal cordz” and may play a role in the elinin ‘ation of transient cortical projections to this structure. Thus, there is strong circumstantial evidence in both the species in which selective axonal elimination has been most thoroughly demonstrated, that a specific type of glial cell may play a role in the elimination of processes. However, this demonstration points to, rather than answers, the most intriguing question; what marks an axonal process which is to be eliminated? The role of gitter cells in this process could be either an active or passive one. Gitter cells may be able to identify inappropriate axonal processes and remove them or thkir role may be passive and limited to removal of processes
Reading list 1 Innocenti, G. M., Fiore, L and Caminiti, R (1977) Neumsci Lert 4, 237-242 2 Innocenti, G. M. and Can&it& R (1980)
Exp. Brain Res. 38, 381-394 3 Ivy,
G.
0. and Killackey,
H. P. (1981)
J.
Comp. NewvL 195, 367-389 4 Killackey,
H P. and Chalupa,
L (1984)
Anat
Ret 208,93A-94A 5 Bates,
C. and Killackey,
H. P. (1984)
Dev.
Bruin Res 13,265-273 6 Stanfield, B. B., O’Leary, D. D. M and Fricks, C. (1982) Nature(London) 298,371-373 7 Tolbert, D. L and Panneton, W. M. (1983)J.
Comp. NeumL 221,216-228 8 Innocenti, G. M. (198 1) Science 212, 824827
9 O’Leary, D. D. M., Stanfield, B. B. and Cowan, W. M. (1981) Dev. Bmin Rex 1, 607417 10 Ivy,
G.
0. and KilIackey,
Ii.
P. (1982)
J.
Neumsci 2,735743 11 Stanfield, B. B. (1984) lYena!sNeurosci 7,3741 12 Innocenti, G. M, Clarke, S. and Koppel, I-L (1983) Dev. Brain Res 11, 39-53 13 Innoce’nd, G. Id, Clarke, S. and Koppel, I-L (1983) Dev. Bmin Res 11,5546 14 Russell, G. V. (1962) Tex Rep Biol Med 20, 338-351 15 Cammenneyer, J. (1970) Neumsci Res 3,43-
129 16 Liig E. A. (1976) J. AnnL 121,29-45 17 Ling, E. A. (1977) 1 AnaL 123,637-648 18 Ivy, G. 0. and Killackey, H. P. (1978) Bmin Res 158,213-218 19 Valentine, K. L and Jones, E. G. ( 198 1) Anat EmbryoL 163, 157-172 20 Ling, E. k (1976) Acta AnaL 96,600-609 HERB
P. KILLACKEY
Department of Psychobiology, University of Califomia, Irvine CA 92717, USA
anism underlying orderly motor-unit recruitment Although the size principle was initially postulated from observations on the stretch and flexor reflexes in decerebrate and spinal cats, subsequent evidence has enabled Henneman to widen the applicability of the size principle to other movements, including those considered Despite initial formulation over a quarter of a century ago, Henneman’s ‘size by Denny-Brown and Pennybacker, such principle’ remains a provocative concept. Evaluation of the size principle has that it can be currently stated as:
I Henneman’s ‘size principle’: current issues
focused on testing the possibility that motoneuron size is the basis for orderly motor-unit recruitment during the graded development of muscleforce Although the results have been largely inconclusive, these efforts have been central to our understanding of motor-control mechanisms. This article provides an assessment ofthe relevance ofthe ‘sizeprinciple’ to ourcurrent understanding of motorcontroL
The motor unit (an a;motoneuron, its axon and the muscle fibers it innervates) represents the functional quantum by which the nervous system regulates the development of muscle force. This regulation occurs by concurrent variation in the number of active motor units and their rate of activation. The relationship between motor-unit recruitment and activation-rate modulation undoubtedly varies between muscles but the result is always an ability to finely grade muscle force, particularly at low forces. Since a single muscle can comprise hundreds of motor units (e.g. the tibialis anterior muscle in man has about 445 motor units), the task of determining the sequence of motorunit recruitment could be onerous. However, this process does not appear to be one of independent control of motor units by some supraspinal center because the number of combinations by which even 300 motor units could be recruited exceeds the number of cells in the brain Rather, mechanisms have evolved at the spinal level which dictate the sequence of motor-unit recruitmenf a phenomenon 0 1984. Elsevier S&m
F’ublishm B.V.. Amsterdam
referred to as orderly recruitment ‘ . . . a particular voluntary movement appears to begin always with discharge of the same motor unit More intense contraction is secured by the addition of more and more units added in a particular sequence. . . . This ‘recruitment’ of motor units into willed contraction is identical with that occurring in certain reflexes. . . The early motor units in normal gradual voluntary contraction are always in our experience small ones. . . . The larger and more powerful motor units, each corn& ling many more muscle fibres, enter contraction late.’ Denny-Brown and Pennybacker, 1938 ’ These observations of Denny-Brown and Pennybacker on the organized nature of motor-unit recruitment (cumulative activation) have withstood the test of time, having been examined in many laboratories with a wide variety of paradigms, muscle groups and animal speci&. Much of this evaluation has been undertaken since 195 7, when Hemreman proposed a ‘size - principle’ as the mech
0378 - 5912/84/SZ.W
‘The amount of excitatory input required to discharge a motoneuron, the energy it transmits as impulses, the number of fibres it supplies, the contractile properties of the motor unit it innervates, its mean rate of firing and even its rate of protein synthesis are all closely correlated with its size. This set of experimental facts and interrelations has been called the “size principle”.’ Henneman, 1 9774 That is, Henneman suggests that the orderly recruitment of motor units is due to variations in motoneuron size (i.e., surface area of the soma and dendrites); the motor unit with the smallest mote neuron is recruited first and the motor unit with the largest motoneumn is recruited last Although seemingly straightforward such a statement highlights the two central efferent issues of the size principle which remain unsolved: What size-related mech anism(s) produces orderly recruitment and in which group of motor units does the size principle operate for a specific task? The mechanism issue
While orderly recruitment appears a robust phenomenon within spified limits, no consensus exists on the mechanism responsible for establishing the functional
TINS - JuIy 1984 Reading list Clarke, J. D. W., Hayes, B. P., Hunt, S. P. and Roberts, A. (1984) J. PhysioL (London) 348, 51 l-525 Freud, S. (1877) Sber. Akad Wiss Wien 75, 15-27 Rohon, V. (1885) Sber. Bayer Akaa! Wiss. Math 14, 39-51 Beard, J. (1889) Proc R Sot (London) 46, 108-118 Lamborghini, J. E. (1980) J Camp. NeuroL 189,323-333 Coghill, G. E. (1914) J Camp. NeuroL 24, 161-234 Hughes, A (1957) J; Anat 91, 323-338 Roberts, A and Hayes, B. P. (1977) Proc R Sot London Ser. B 196,415-429 Roberts, k and Clarke, J. D. W. (1982) Phil
10 11 12 13 14 15 16 17 18
Trans. R Sot London Se,: B 296, 195212 Kahn, J. k and Roberts, A. (1982) Philos. Trans R Sot London Ser. B 296,229-243 Roberts, A and Smyth, D. (1974) J Camp. . PhysioL 88, 3142 Kahn, J. A and Roberts, A (1982) 1 Exp. BioL 99, 185-196 Roberta, A and Stirling, C. A (197 1) Z. VgL PhysioL 71,295-310 Jacobson, M. (198 1) J; Neurosci 1,9 18-922 Jacobson, M (1981) .X Neurosci 1, 923-927 Harrison, R G. (1910) J. Exp. Biol 9, 787848 Roberts, A and Taylor, J. S. H (1982) J EmbryoL Exp. MolphoL 69,231-250 Taylor, J. S. H. and Roberts, A (1983) 1 EmbryoL Exp, MorphoL 75,49-66
Glia and the elimination of trahsient cortical projections Over thepast decade a number ofstudies have demonstrated that during the course of development, corticalprojection neurons undergo major changes in their areai distribution In particular, the distribution of neuronsprojecting to agiven target is much wider in the infant than in the adult This wasfirst demonstratedfor callosal projection neurons in the visual system of the cat’, but since then the observation has beeriextended to callosalprojections of the somatosensory system of the cap, rat’ and monkeyi There is also evidence that similar changes occur in the distribution Of cortical neurons which project sub-cortically 5-7. Other evidence obtained utilizing retrograde double labelling techniques, has suggested that these changes are accomplished not by the elimination of neurons (‘cell deathy0,9 but by the selective elimination of neuronal prqcesses’4 These findings, which were treated in detail in a recent review in TINS by Stanfield”, raise the intriguing question of how axonalprocesses are selectively eliminated dun’ng the course of development.
.
Recently, Innocenti and coworkers pro- their existence coincides with the time vided evidence that a specific type of glial period during which callosal axonal pr@ cell plays a role in the selective elimination cesses are eliminated Third, Innocenti of cortical projections’2,L3. They refer to and collaborators present electron microthis transient cell type as a gitter cell, a graphic evidence of gitter cells surrounding term which, according to Russell, was and presumably engulfing axonal pre introduced by Nissl in 1904 to describe cesses, and of gitter cell vacuoles that phagocytes14. Innocenti et al! chose this contain degenerative debris. In this regard, term for the cell they described in the the gitter cells have been demonstrated by occipital cortex of the cat because it is others to have a number of the characterrelatively free from pre-existing corm* istics of macrophages (see below). Pertations - the literature on CNS phage haps the strongest, although still somecytes is bewildering in its complexity and what indirect, evidence of gitter cell use of synonymsU. The intriguing properinvolvement in axonal elimination, is the ties of the gitter cell, with respect to demonstration by Innocenti and coaxonal elimination, are as follows. First, workers that the clusters of these cells they are found in clusters in the cortical accumulate horseradish peroxidase followwhite matter in regions through which ing injection of this substance into the transient callosal axons must normally opposite hemisphere. Presumably the err travel One cluster in particular, the dorse zyme is not acquired directly by transport medial, is situated in such a position that through gitter cell processes, but is secon& trtisitory axons pass through it on the ary to the phagocytosis of eliminated and way to and from the medial portion of degenerating HRI-labelled callosal axons primary visual cortex (an area which by gitter cells. However, this remains to loses callosal projection neurons)...Second, be directly demonstrated the existence of the gitter cell clusters is The observations and interpretation? of short lived In the cat, they are found only Innocenti and his coworkers are strongly during the first postnatal month Thus, supported by similar observations on the
19 Bixby, J. L. and Spitzer, N. C. (1984) Dev. BioL (in press) 20 Lamborghini, J. E., Revenaugh, M and Spitzer, N. C. 11979) .I Coma. NeuroL 183.741-152 21 Spitzer, N. C. (1983) &DevelopingandRegenersting Vertebrate Nervous Systems (Coates, P. W., Markwald, R R and Kenny, A D., eds), pp. 41-59, Alan R Liss, Inc., New York 22 Blair, L A C. (1983) J. Neurosci 3, 143O1436 23 O’Dowd, D. K. (1983) Nature (London) 303, 619-621 24 Katz, M J. and Lasek, R J. (I 979) J Comp. NeuroL 183, 811-832 25 Lamborghini, J. E. (198 1) Sot Neurosci Abstr 7,291 NICHOWS C. SPITZER Department of Biology, Universiv of California, San Diego, La Jolla, CA 92093, USA .
I
gliai cells in developing rat’s neocortex. Ling described clusters of what he called ameboid microglia in the region of the corpus callosum of the neonatal rat as well as electron micrographs of these cells engulfing unmyelinated axonal process&. In another report”, Ling provided evidence that these cells had some of the histochemical properties of active phagocytes; specifically, they possess high levels of the hydrolytic enzymes acid phosphotase and aryl sulphatase. Ivy andKiIIackey provided evidence that there is a transient population of glial cells in the telencephalon of the neonatal rat which are capable of accumulating horseradish peroxidase18. The location of at least one of these JXRPlabelled glial populations is the same as that studied by Ling and it is in such a position that most callosal axons must pass through it*. Valentino and Jones have confirmed the observations of Ling and provided additional evidence that ameboid micre glia or gitter cells are macrophages by demonstrating that these cells reacted positively to an esterase stain specific to blood monocytes and macrophages and we= also labelled with a monoclonal antibody to macrophage cel&rface polypeptideslg. Another similarity between the gitter cells of the rat and the cat is their transiency. F the rat, clusters of nonneuronal cells, which can be labelled with HRP, are not detectable at the end of the second postnatal week, the time by which *In retrospeq Ivy arid I misinterpreted the HRPlabelling in these glial cells. We assumed that the accumulation of HRP in these cells was the direct result of transport by long glial processes rather than an indirect phenomenon (transport by callosal axon processes which are then engulfed by the gitter cells) as would now seem to be most likely. Thus, it was suggested by Ivy and I that these transient gli& cells may play a role in axonal guidance. However, both the present hypothesis, as well as more recent clear electron microscopic and immunocytochemical evidence that this s&e population pf cells are macrophages make that suggestion very unlikely.
@ 1984. Elrevirr
Science Publishas
RV.. Amsted~
0378 - SPI2/84/S2M)
TINS - July 1984
226
which are degenerating because they have failed to make connections. Undoubtedly, over the next couple of years, there will be much research aimed at answering this question.
the adult distribution of callosal projection neurons is achieved.Finally, it should be pointed out that a similar cell type has been described in the neonatal rat’s spinal cordz” and may play a role in the elinin ‘ation of transient cortical projections to this structure. Thus, there is strong circumstantial evidence in both the species in which selective axonal elimination has been most thoroughly demonstrated, that a specific type of glial cell may play a role in the elimination of processes. However, this demonstration points to, rather than answers, the most intriguing question; what marks an axonal process which is to be eliminated? The role of gitter cells in this process could be either an active or passive one. Gitter cells may be able to identify inappropriate axonal processes and remove them or thkir role may be passive and limited to removal of processes
Reading list 1 Innocenti, G. M., Fiore, L and Caminiti, R (1977) Neumsci Lert 4, 237-242 2 Innocenti, G. M. and Can&it& R (1980)
Exp. Brain Res. 38, 381-394 3 Ivy,
G.
0. and Killackey,
H. P. (1981)
J.
Comp. NewvL 195, 367-389 4 Killackey,
H P. and Chalupa,
L (1984)
Anat
Ret 208,93A-94A 5 Bates,
C. and Killackey,
H. P. (1984)
Dev.
Bruin Res 13,265-273 6 Stanfield, B. B., O’Leary, D. D. M and Fricks, C. (1982) Nature(London) 298,371-373 7 Tolbert, D. L and Panneton, W. M. (1983)J.
Comp. NeumL 221,216-228 8 Innocenti, G. M. (198 1) Science 212, 824827
9 O’Leary, D. D. M., Stanfield, B. B. and Cowan, W. M. (1981) Dev. Bmin Rex 1, 607417 10 Ivy,
G.
0. and KilIackey,
Ii.
P. (1982)
J.
Neumsci 2,735743 11 Stanfield, B. B. (1984) lYena!sNeurosci 7,3741 12 Innocenti, G. M, Clarke, S. and Koppel, I-L (1983) Dev. Brain Res 11, 39-53 13 Innoce’nd, G. Id, Clarke, S. and Koppel, I-L (1983) Dev. Bmin Res 11,5546 14 Russell, G. V. (1962) Tex Rep Biol Med 20, 338-351 15 Cammenneyer, J. (1970) Neumsci Res 3,43-
129 16 Liig E. A. (1976) J. AnnL 121,29-45 17 Ling, E. A. (1977) 1 AnaL 123,637-648 18 Ivy, G. 0. and Killackey, H. P. (1978) Bmin Res 158,213-218 19 Valentine, K. L and Jones, E. G. ( 198 1) Anat EmbryoL 163, 157-172 20 Ling, E. k (1976) Acta AnaL 96,600-609 HERB
P. KILLACKEY
Department of Psychobiology, University of Califomia, Irvine CA 92717, USA
anism underlying orderly motor-unit recruitment Although the size principle was initially postulated from observations on the stretch and flexor reflexes in decerebrate and spinal cats, subsequent evidence has enabled Henneman to widen the applicability of the size principle to other movements, including those considered Despite initial formulation over a quarter of a century ago, Henneman’s ‘size by Denny-Brown and Pennybacker, such principle’ remains a provocative concept. Evaluation of the size principle has that it can be currently stated as:
I Henneman’s ‘size principle’: current issues
focused on testing the possibility that motoneuron size is the basis for orderly motor-unit recruitment during the graded development of muscleforce Although the results have been largely inconclusive, these efforts have been central to our understanding of motor-control mechanisms. This article provides an assessment ofthe relevance ofthe ‘sizeprinciple’ to ourcurrent understanding of motorcontroL
The motor unit (an a;motoneuron, its axon and the muscle fibers it innervates) represents the functional quantum by which the nervous system regulates the development of muscle force. This regulation occurs by concurrent variation in the number of active motor units and their rate of activation. The relationship between motor-unit recruitment and activation-rate modulation undoubtedly varies between muscles but the result is always an ability to finely grade muscle force, particularly at low forces. Since a single muscle can comprise hundreds of motor units (e.g. the tibialis anterior muscle in man has about 445 motor units), the task of determining the sequence of motorunit recruitment could be onerous. However, this process does not appear to be one of independent control of motor units by some supraspinal center because the number of combinations by which even 300 motor units could be recruited exceeds the number of cells in the brain Rather, mechanisms have evolved at the spinal level which dictate the sequence of motor-unit recruitmenf a phenomenon 0 1984. Elsevier S&m
F’ublishm B.V.. Amsterdam
referred to as orderly recruitment ‘ . . . a particular voluntary movement appears to begin always with discharge of the same motor unit More intense contraction is secured by the addition of more and more units added in a particular sequence. . . . This ‘recruitment’ of motor units into willed contraction is identical with that occurring in certain reflexes. . . The early motor units in normal gradual voluntary contraction are always in our experience small ones. . . . The larger and more powerful motor units, each corn& ling many more muscle fibres, enter contraction late.’ Denny-Brown and Pennybacker, 1938 ’ These observations of Denny-Brown and Pennybacker on the organized nature of motor-unit recruitment (cumulative activation) have withstood the test of time, having been examined in many laboratories with a wide variety of paradigms, muscle groups and animal speci&. Much of this evaluation has been undertaken since 195 7, when Hemreman proposed a ‘size - principle’ as the mech
0378 - 5912/84/SZ.W
‘The amount of excitatory input required to discharge a motoneuron, the energy it transmits as impulses, the number of fibres it supplies, the contractile properties of the motor unit it innervates, its mean rate of firing and even its rate of protein synthesis are all closely correlated with its size. This set of experimental facts and interrelations has been called the “size principle”.’ Henneman, 1 9774 That is, Henneman suggests that the orderly recruitment of motor units is due to variations in motoneuron size (i.e., surface area of the soma and dendrites); the motor unit with the smallest mote neuron is recruited first and the motor unit with the largest motoneumn is recruited last Although seemingly straightforward such a statement highlights the two central efferent issues of the size principle which remain unsolved: What size-related mech anism(s) produces orderly recruitment and in which group of motor units does the size principle operate for a specific task? The mechanism issue
While orderly recruitment appears a robust phenomenon within spified limits, no consensus exists on the mechanism responsible for establishing the functional