The Origin, Course and Terminations of Corticospinal Fibers in Various Mammals

The Origin, Course and Terminations of Corticospinal Fibers in Various Mammals JEAN ARMAND

Studies spanning a period of more than 20 centuries ultimately culminated in the discovery of the pyramidal decussation (cf. Thomas, 1910) in the middle of the 19th century. The first step in these studies was made by Hippocrates (460-380 B.C.), who noted in his “lri,juric>.sof the H c w l ” : “and for the most part convulsions seize the other side of the body ; for if the wound be situated on the left side, the convulsions will seize the right side of the body.” But. it was not until the end of the first century that a second step was achieved by Aretaeus of Cappadocia, who suggested an anatomical explanation for crossed motor disorders : “The cause of this is the interchange in the origin of nerves, for they do not pass along on the same side, the right on the right side, until their terminations; but each of them passes over to the other side from that of its origin, decussating each other in the form of the letter X . ” A third step contributed by the “Age (~EnlighteririIerit’’eventually casted some light on the anatomical substrate of the pyramidal decussation. The leading author in this respect was Mistichelli (1709) of Pisa, who described it in the flowery style of his time: “The medulla oblongata is on the outside interwoven with fibers, which by their criss-cross superposition, resemble a woman’s braid, whence it comes that many nerves which branch out on one side, have their roots on the other.” One year later Pourfour du Petit (1710) of Montpellier, studied the pyramidal decussation using a 3-fold (clinical, experimental and anatomical) approach. In his patients, he observed first that the lesion of one hemisphere produced a contralateral paralysis. In the dog, he therefore made experimental lesions in the central part of the hemisphere. In all cases, he noted a contralateral paralysis as in his patients. Finally, he described the anatomical structure which seemed to be responsible for this functional crossing in the following terms : “each pyramidal body divides at its inferior part into two large handfuls of fibers, more often three and sometimes four. Those of the right side pass to the left and those of the left side pass to the right.” During the 18th century, this description of the pyramidal decussation was confirmed by Von Haller ( 1754) and Vicq d’Azyr ( 1 786). It was not until one century after Pourfour du Petit that Gall with his pupil Spiirzheim (1810) made the next important contribution to the anatomy and the physiology of the pyramidal tract. By means of their method of dissection, they were able to recognize the fibers involved in the decussation (Fig. I ) . Then, working up to the cerebral cortex, thinking that some fibers from the central region descend through the pyramidal decussation, they called them motor fibers. The two founders of the theory of phrenology mainly left us with one of the first pictures of the pyramidal decussation. These two tireless public speakers, in diffusing throughout Europe their erroneous “localizationist” theory, also disseminated a rather clear-cut concept of the pyramidal tract, which concept had gradually emerged over a period of 20 centuries. First the lesion of one side of the

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Fig. I . One of the first pictures of the pyramids (plate V of Gall and Spiirzheim ( I 8 10); reproduced with the kindest permission of the library of the Lyon Medical Faculty). “Pour faire voir distinctement le veritablement entrecroisement, il n’est pas besoin de macCration ou de toute autre preparation, ainsi que le croyait Santorini. I1 suffit d’enlever avec precaution la membrane vasculaire au commencement du grand renflement, ou immtdiatement en bas de I’extremitk inferieure des pyramides. Pour cela on fait i cette membrane une incision si ICgkre que les cordons nerveux qui se trouvent au-dessous ne soient pas offenses. Puis on Ccarte tout doucenient les deux bords de la ligne mediane, sans les tirailler ni les dechirer. A peine les deux bords sont-ils un peu Cloignks I’un de I’autre, que l’entrecroisement frappe les yeux. Les petits cordons des pyramides ne forment pas un veritable entrecroisement, ils s’entrecoupent et passent les uns sur les autres. seulement dans une direction oblique.”

brain had been seen to induce paralysis in muscles on the other side of the body. Then the explanation for this functional crossing was suggested to be the decussation of the nervous pathway responsible for motricity. Finally, the gross anatomy of this pathway, from the cerebral cortex to the medullary pyramids and their decussation before descending into the spinal cord, was suggested by dissection. Later on, the origin, course and terminations of the pyramidal tract were examined in succession.

33 I

(I) THE CORTICAL ORIGIN OF THE PYRAMIDAL TRACT- A HISTORICAL SURVEY ( A ) Dcfi’nition of the pysarnicld trtrct psior to the discovery of the neuron

The question as to where the pyramidal tract actually originates could naturally only be settled after the discovery of the neuron. However, during the years prior to the formulation of the neuron theory by CaiaI in 1888. three authors played an important role and therefore should be mentioned. First, Turck defined the pyramidal tract through his studies in human pathological anatomy. Then Gudden proved indirectly the cortical origin of its corticospinal c o n ponent by the secondary experimental degeneration method. Flechsig, at last, confirmed these results by investigating myelination during ontogenesis. Turck, in 1851, was the first to use the term of “Pyramidenstrang” to designate the set of nerve fibers passing through the medullary pyramids (cf. Morin, 1951). He noted that lesions in the spinal cord resulted in some changes in the white matter caudal to the lesion. In light of this. he deduced from his observation after lesion of the medullary pyramids that its fibers continue into the cord as a crossed tract and an uncrossed tract, the latter of which is still called the “Turck tract.” Although he recognized that some of these fibers originate in the cortex, he thought that they arose mainly in the basal ganglia. Strictly speaking, this definition of the pyramidal tract did not take into account the origin of its fibers. for the relationship between the nerve fiber and the cell body was not yet established. To appreciate the state of knowledge during this first half of the 19th century, one must recall the type of methods used to examine the nervous system at that time (cf. Dejerine, 1895). Nervous tissue was dissected mechanically with the aid of needles or chemically by dissolving the interstitial tissue, and was then observed first with lenses and later with low power microscopes. Myelinated nerve fibers and nerve cell bodies were first discovered in the white and the grey matter respectively. They were regarded to constitute a continuous reticular net. Von Gerlach’s network theory could be summarized as follows : “Les expansions protoplasmiques se resolvent en un rkseau de mailles serrkes comprenant toute la substance grise, et les travkes de ce reseau, se reunissant a nouveau, reconstituent des fibres nerveuses qui vont a la substance blanche et s’y continuent avec les tubes nerveux mCdullaires” (Cajal, 1909, 1 954). During this period of confusion, Gudden ( 1872) suggested from experimental studies in the dog that the medullary pyramids arose within the cerebral cortex and distributed to the spinal cord. After lesions of the sigmoid gyms in puppies, sparing the striatum, he noted a complete “atrophy” of the ipsilateral pyramid, the course of which could be followed into the contralatera1 lateral spinal funiculus. However, it was only with Forel (1 887) that it was realized that the methods of Waller ( 1850) and Gudden both showed degeneration of some “fiber system” after lesions of some “grey focus,” and that their difference is quantitative more than qualitative because Gudden used young animals with a more intense metabolism than the adults used by Waller. At that time the importance of this basic experiment by Gudden was not recognized. The conceptual framework of the neuron theory was not yet developed sufficiently to correlate the lesion of one part of the nervous system with the degeneration of another. Confirmation of the results of Turck and Gudden was provided by Flechsig (1876) regarding thc corticospinal component of the pyramidal tract and its cortical origin. Flechsig’s method is based on the successive myelination of various spinal funiculi during fetal life and after birth. The myelin sheath is stained in black by osmic acid, and this revealed the unmyelinated dorsolateral and ventral corticospinal tracts in the corresponding funiculi of fetal spinal cord. Flechsig assumed that these funicular tracts which myelinated at a later stage contained fibers

332 of the same origin, course and target, as those shown by the degeneration findings of Tiirck and Gudden. Although this method of myelin staining gave clear results, it was not without its limitations when used for long fibers such as those in the corticospinal tract. Dejerine ( 1895) made this reservation : “il peut arriver que la partie de ces fibres voisine de leurs cellules d’origine, soit deji revttue de myeline, alors que la pCripherie en est encore depourvue et on pourrait par consequent &tre amen6 a croire, que cette partie pCriphCrique n’appartient pas au mtme systeme que celui que I’on Ctudie.” Thus, initially, Flechsig shared Turck’s opinion on the striatal origin of the pyramidal tract. However, around 188 1 , he could trace pyramidal fibers back into the internal capsule. Finally, the observation on the myelination of the cerebral cortex by Parrot (1 879) and Flechsig ( 1889) led them to identify the true origin of corticospinal fibers. This was based on the observation that in man between the second and the third week after birth myelinated fibers appear as a white trail starting at the sulcus of Roland0 and proceeding into the internal capsule. ( B ) The neuron the or^ und its contribution to neumanatomical techniques The above studies were published before the formulation of the concept that there exist individual neurons rather than a reticular net. However, the above studies contain all the data from which the concept of the neuron could be synthesized. First the pyramidal tract was recognized as a well circumscribed “fiber system” at the level of the medullary pyramids. Then, its caudal and rostra1 course were revealed. Finally its presence at the cortical level led to the inference of its discrete origin. All the experimental data were present to define the pyramidal tract and particularly its corticospinal component. One main element was missing to interprete these experimental data correctly, i.e., the concept of the neuron. It was left to Cajal to synthesize this principle from the accumulation of data: “Des 1888, . . . , nos recherches, faites prkistment avec la methode m&me de Golgi dans les territoires les plus divers du systeme nerveux, nous ont amene ... aux constatations capitales suivantes .. . La cellule nerveuse avec tout I’ensemble de ses divisions et subdivisions constitue donc une individualit6 absolument independante et, pour employer l’expression de Waldeyer, nous I’appellerons neurone” (Cajal, 1909). In practice, the new concept of the neuron, with its cell body, its axon and collaterals, and its terminations, gave new relevance to the neuroanatomical techniques of that time: the Waller technique ( 1 850) for the study of the nerve fiber, the Nissl technique (1885) for the study of the nerve cell. “Nous pourrions formuler la loi de Waller en ces termes plus exacts: la conservation de la vie du cylindre-axe et des expansions dendritiques est intimement like au maintien des connexions naturelles de ces prolongements avec le noyau .. . Etant un produit du cylindre-axe, la p i n e mydinique est, par suite, dans une etroite dependance vitale et nutritive avec lui ... ; et lui mort, elle se detruit. Le cylindre-axe interrompu avant la naissance de ses premikres branches ne pouvant plus se regenerer, sacellule d’origine ... ne fonctionne plus . . . et s’atrophie par la suite” (Cajal, 1909). In light of the neuron theory the techniques for studying myelinated fibers. as well as those for studying cell body, took on a new meaning. ( C ) The Betz cells as origin of the pyramickil truci

The observation of the “retrograde chromatolysis” in cell bodies of neurons, the axons of which have been sectioned, i.e., the Nissl (1894) retrograde degeneration method, soon proved to be the best approach for locating the cell bodies of origin of a given neural pathway.

333 In 1909, Holmes and May, using this method, published their article “On the exact origin of the pyramidal tracts in man and other mammals.” Holmes and May. however, were not the first to use the “retrograde chromatolysis” technique to study the pyramidal tract. Ten years before, it was employed in anatomopathological cases with lesions of the internal capsule (Dotto and Pusateri, 1897; Von Monakow, 1897 ; Marinesco, 1899) as well as in experimental cases with subcortical lesions of motor cortical projection fibers (Ballet and Faure, 1899). The cells of origin revealed by this method were not only the pyramidal tract cells. However, Von Monakow (1897) believed that the pyramidal tracts originate in the giant pyramidal elements (Riesenpyramidenk6rpern) of the central convolutions. In cases of paraplegia induced by spinal lesions, Marinesco ( I 899) described chromatolysis in the Betz cells of the upper third of the precentral gyrus and the lobulus paracentralis. This author summarized the experimental data obtained by this “retrograde chromntolysis” technique : “Les lesions de la capsule interne provoquent des alterations rapides des grosses cellules pyramidales, alterations qui aboutissent a l’atrophie de ces cellules . . . Par contrc la ICsion est beaucoup plus lente et moins accusee lorsque ce faisceau pyramidal est dCtruit dans la moelle . . . I1 est permis de conclure . .. que la lesion des grosses cellules pyramidales aprks les lesions du faisceau pyramidal est un fait sQr et certain que les examens negatifs ne peuvent infirmer.” Holmes and May performed hemiscctions at a high cervical level (CI) in different mammals. They further examined pathological cases of spinal lesions at a low cervical level (C7) as well as cases of lesions in the internal capsule. After a survival time varying from 5 to 157 days in the experimental cases and from 108 to 229 days in the pathological cases, the cell populations in symmetrical areas of the intact and affected hemispheres were compared in serial Nissl-stained sections. I n cat, the cortical zone containing affected cells was found to extend over the pericruciate area. The percentage of intact giant cells in the affected hemisphere as compared to the intact hemisphere is 5--6% on the interhemispheric surface and 2-3% on the surface of the hemisphere. In monkey, according to Holmes and May the cortical zone containing affected cells includes only the precentral area. The percentage of intact giant cells in the affected hemisphere as compared to the intact one is never more than 8 % . In monkey as in cat, the only cells which are affected are the giant cells of the infragranular layer. In addition, many of the giant cells seemed to have disappeared. An important aspect of Holmes and May’s paper is the fact that the results were obtained in carnivores (cat, dog). prosimians (lemur), gyrencephalic monkeys (Cercopithecus, Mucucu.s r h ~ s u s )chimpanzee , and man. However, in their discussion they assumed that the Betz cells were the sole origin of the pyramidal tracts in all mammals. The paper of Holmes and May was especially important because it was published at the time when Griinbaum and Sherrington (1901) had just shown that the excitable cortex in some monkeys and apes was restricted to the precentral region. In addition, in 1905 Campbell defined the cytoarchitectonic precentral area by the presence of Betz cells. On examining some monkey brains used by Griinbaum and Sherrington, he further equated the “excitable cortex” of these animals with the precentral area (or area 4 of Brodmann, 1909). Thus these three, electrophysiological, cytoarchitectonic, and neuroanatomical, studies combined gave the evidence for a clear relationship between structure and function. The Betz cells, defining the cytoarchitectonic area of the motor cortex, were identified as being the sole cells of origin of the pyramidal tract. “The importance of this subdivision of the cortex by histological methods lies in the fact that from difference in structure we may infer some difference in function, and a

334 structural subdivision thus becomes parallel to a functional” (Holmes and May, 1909). The last word on the Betz cells as the sole origin of the pyramidal tract was said by Lassek in a series of articles published between 1939 and 1948 (Lassek, 1954). Lassek (1942b) first reproduced the Holmes and May’s experiment by making a spinal hemisection at a high cervical level (C1) in monkey (Mucacu mukrrra). In his analysis he paid attention, not only to the cortical cells, but also to the pyramidal fibers both proximal and distal to the spinal lesion. Distal to the lesion, the corticospinal fibers degenerate and disappear completely after a survival time of 1-10 months. Proximal to the lesion, the pyramidal fibers do not exhibit any sign of degeneration. In these cases of spinal hemisection, the number of fibers in both medullary pyramids is similar. Other authors (Faure, 1899; Schroder, 19 14; Tower, 1940) had previously noted that the pyramidal fibers proximal to the spinal lesion remained. This was also pointed out by Dr. Howell, pathologist at the National Hospital, on the day of the communication by Holmes and May of their results at the Royal Society of Medicine on 25 February 1909 (cf. Lassek, 1948): “I should like to ask Dr. Holmes how he would explain the survival of the axis-cylinder after the disappearance of the cell from which he had assumed that it arose.” The answer is given by Lassek more than 30 years later: “I believe the retrograde method fails to prove that the so-called Betz, or giant, cells give sole origin to the pyramidal tract fibers” (Lassek, 1942b). The retrograde degeneration method which was thought to be the best suited approach for identifying the cells of origin of a nervous pathway thus proved unsuitable for the pyramidal tract. Although the retrograde chromatolysis is clearly seen in the largest cortical cells, it is more difficult to discern in the small ones (Pernet and HeppReymond, 1975). Also, after axotomy at increasing distance from the cell body, the retrograde changes become progressively less pronounced (Molenaar et al., 1974). Finally, the great number of axon collaterals of the pyramidal fibers, particularly at brain stem level, could explain the preservation of the proximal part of the pyramidal fibers after a spinal lesion (Tower, 1940; Walshe, 1942; Barron and Dentinger, 1979; Dentinger et al., 1979).

( D ) The cortical (.~roarchitectoriiccirea~of origin of rhr pyramidul tract

Notwithstanding Lassek’s criticisms, the use of the retrograde degeneration method established that the giant pyramidal cells located in the fifth layer of area 4 participate in the origin of the pyramidal tract in mammals. Yet one outstanding question remained: what percentage of the pyramidal fibers is derived from these Betz cells? Lassek answered this question by comparing the number of pyramidal fibers at a level just rostra1 to the decussation with the number of giant cortical cells in an intact hemisphere. In man, 1,000,000fibers can be counted in one pyramid (Lassek and Rasmussen, 1939), whereas only 34,000 giant cells are present in one hemisphere (Lassek, 1940; 25,000 according to Campbell, 1905), each cell measuring between 900 and 4100 pm2. Thus, there are 30 times more pyramidal fibers than Betz cells. Let us assume that the largest cells give rise to the largest diameter axons (Szentagothai, 194 1 ; Hamada et al . , 198 1 ) . In that case, the Betz cells in man would give rise to only 2-3 % of the pyramidal fibers, probably those of 10 pm or more in diameter. In monkey (Lassek, 1941) and cat (Lassek and Rasmussen, 1940) similar ratios were obtained by the counting method. The fiber counting method thus showed that the Betz cells are the origin of relatively few pyramidal axons. It also showed, in conjunction with various cortical lesions, that cortical areas other than area 4 give also rise to pyramidal tract fibers.

335 ( I ) 111 m i n The exact origin of pyramidal fibers remains unknown, and more anatomopathological data are needed. I n a case of surgical ablation ofthe precentral gyrus, which occurred 20 years prior to the patient death, the ipsilateral medullary pyramid contained 40%’ of its fibers still intact (Jane et al., 1967). Thus, area 4 could be the origin of approximately 60% of the pyramidal fibers, whereas the remaining 40% may arise from other cortical areas. These quantitative results confirm the classical anatornopathological descriptions. In all cases of cortical lesions followed by secondary degeneration (“sclerose descendante”) of the pyramidal tract, Charcot ( 1 876) noted that the lesion always included either the precentral convolution or the postcentral one or both in combination with the adjoining parts of the parietal and frontal lobes (Dejerine, 1895). Flechsig ( 1889) came to the same conclusion on the basis of his myelination studies during ontogenesis. The thus accepted view of both a pre- and postcentral origin of the pyramidal tracts was emphasized by the fiber counting method in conjunction with anterograde degeneration technique. ( 2 ) I n morikc\. After localized cortical ablations. Russell and De Myer (1961) also counted the number of pyramidal fibers at the medullary level. In comparing the number of intact fibers in the affected pyramid with that in the normal one. they deduced the percentage of fibers arising in the lesioned cortical area. This method. however, is only possible when using a 6 1 2 month survival time. thus allowing the degeneration of all the fibers from the lesioned cortex. Under these conditions. 3 I R of the pyramidal fibers were found to originate in the cytoarchitectonic area 4, 29% in area 6 and 40%’ in the parietal cortex (Fig. 2). These data are in slight Area 4 31 7.

Area 6 : 29%

:

Areas 3,1,2,5,7:

Fig. 2 . The cortical origin and percentages of pyramidal tract fibers originating in the various architectonic areas in M ~ X ~ Yrhcsus L A (modified from Russell and De Myer, 1961).

disagreement with those of Haggqvist 11937) who estimated that 415 of the pyramidal fibers arose from area 4 . Previously, the contribution of the parietal cortex to the pyramidal tract had been emphasized by secondary degeneration findings (Minkowski, 1924; Uesugi, 1937). Peele (1942). particularly, identified the cytoarchitectonic areas 3 , 1, 2, 5 , 7 as giving rise to pyramidal fibers. This extension of the origin of the pyramidal tract beyond the gigantocellular area 4 weakened the conclusions of Holmes and May. In fact Levin and Bradford ( 1 938), using also

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the retrograde degeneration technique, came to a different conclusion than Holmes and May and observed chromatolysis mainly in the cells of area 4, but to a lesser extent also in neurons of areas 5, 3, 2 and tentatively in area 1.

(3) In cut The fiber counting method has shown that the cortical origin of the pyramidal tract may extend outside area 4. In carnivores, the medial lemniscus adjoins the dorsal aspect of the pyramid at a level just rostral to the decussation (Verhaart et al., 1964). At this level, it is difficult to distinguish pyramidal fibers from lemniscal fibers. This difficulty may explain the variations in the number of pyramidal fibers obtained at different levels (Van Crevel and Verhaart, 1963a). At a level just rostral to the pyramidal decussation, Lassek and Rasmussen (1940) counted 186,000 fibers, whereas at low medullary level Van Beusekom (1955) counted from 40,000 to 80,000, and Glees (1961) 70,000. At a middle medullary level, where the pyramidal tract is well circumscribed, Van Crevel and Verhaart (1963a) counted an average of 80,000 (from 56,000 to 106,000 in 30 cats) (Fig. 3). The pyramidal tract in the cat, as in man and monkey, contains a minority (2%) of large diameter fibers (>6 pm).The majority (90%) of the cells of origin of these large fibers are located in the cortical region containing area 4. In other words, the giant cells of area 4 in cat constitute only 2 % of corticospinal cells. Many other cells of the primary sensorimotor cortex are at the origin of the small and medium diameter fibers. The contribution of the fiber counting method in determining the origin of the pyramidal tract has not been without its limitations. The first attempts to count pyramidal fibers after cortical lesions led to the conclusion that more than 50% were of unknown origin (Haggqvist,

I NORMAL

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73

20

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60

65

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90

15

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35

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LESION A

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Iaxans LESION 6

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Fig. 3 . Percentages of pyramidal tract fibers of various diameters originating in different cortical areas in the cat (cf., Van Crevel and Verhaart, 1963a,c).

331 1937; Lassek. 1942a: Tower, 1949; Bucy, 1957). In fact, this error lies in a failure to appreciate the degeneration phenomenon (Glees, 1948; Morin et al., 195 1 ; Russell and De Myer. 1961 ; Van Crevel and Verhaart. 1963b). Large myelinated fibers degenerate niorc quickly than thin ones ; however, they are resorbed more slowly. Thus, if the degeneration time is not long enough, many thin fibers will appear “intact”. Russell and De Myer (1961) in monkey and Van Crevel and Verhaart in cat ( 1 963b) therefore chose rather long survival times. (11) THE COURSE AND DISTRIBUTION OF PYRAMIDAL FIBERS

Having first illustrated how via the tortuous historical path the cortical origin of the pyramidal tract was established, we will now deal with the more recent findings and follow the course of the pyramidal fibers from the cerebral cortex to their spinal terminations in various mammals. In general. in all the mammals studied. fibers connecting the cortex with the spinal cord follow a similar C O I I ~ S PThey . descend from the cortex through the internal capsule into the ipsilateral cerebral peduncle. Caudally, they traverse the pontine grey towards the lower brain stein (Noback and Shriver. 1966). At the level of the medulla oblongata, the fibers generally constitute a circumscribed tract along the ventral aspects of the brain stem, i.e., rostra1 to the pyramidal dccussation.

In some ungulates, e . p . , the sheep (Bagley, 1922), goat (Noorduyn, 1959; Haarsten and Verhaart, 1967). horse, cow and pig (Verhaart and Sopers-Jurgens, 1957). a bundle of cortical fibers leaves the cerebral peduncle and courses caudally through the ipsilateral mesencephalic and pontine tegmentum. This corticotegmental tract or Bagley bundle (1 922) originates in the same area as the pyramidal tract. In addition, the fiber diameter spectra of both these tracts are similar (Noorduyn, 1959), the fiber diameters ranging from 1 to more than 6 p m . About 88 % of the fibers have a diameter of 2 pni or less while a majority have a diamter of 1 p m or less (Verhaart and Noorduyn. 1961). According to anterograde degeneration findings in the goat (Haarsten and Verhaart, 1967) the Bagley bundle terminates mainly in the ipsilateral lateral tcgmcntum of the lower brain stem. However, some fibers also terminate in the ipsilateral spinal trigeminal nucleus and in the hilus of the dorsal column nuclei. I n contrast to more evolved species of mammals, as the cat, the pyramidal tract itself in the goat does not distribute fibers either to the spinal tripeminal nucleus o r the lateral tegmentum, which structures are the recipients of fibers from Bagley bundle. Thus, as stated by Towe ( 1 973a), “the combination of pyramidal tract and Bagley bundle in the goat begins to resemble the pyramidal system of carnivores.” Some fibers following the same course as the Bagley bundle are also found in the opossum (Martin et al.. 197.5) and rat (Zimmerman et al., 1964).

( B ) Coirrse r i n d distribution oJ’pyrmiidiiI axon colluterrils within the Imiiri

In their diencephalic, mesencephalic and medullary course, corticospinal fibers are intermixed with cortical fibers terminating in various subcortical cell groups (Kuypers. 1958a,b,c). Moreover, some of these cortical fibers to subcortical structures represent axonal collaterals of corticospinal fibers. Hence, 3 groups of fibers can be distinguished which follow the course of the pyramidal pathway : fibers terminating on cells of origin of descending brain stem

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Fig. 4. Distribution of pyramidal axon collaterals (thick lines) on cells of origin of other descending pathways (Rc, RN, RF), on groups of cells involved in cerebrocerebellar loops (PN, LR), on realy cells of ascending pathways (G, C, V, VB), as well as at different spinal levels. The main internal loops involved in motor regulation are indicated (thin lines). Abbreviations: BG, basal ganglia; C, cuneatus; C b , cerebellum: G. gracilis ;LR, lateral reticularnucleus; MI, primary motor cortex ;0, olive; PN, pontine nuclei; Rc, recurrent collaterals: RF. niesencephalic, pontine, medullary reticular formation; RN, red nucleus ; SI, primary somatosensory cortex ; SII. secondary somatosensory cortex; SC, spinal cord; V , trigeminal complex; VB, ventrobasal complex of the thalamus; VL, ventrolateral nucleus of the thalamus (modified from Wiesendanger, I98 1).

pathways, fibers terminating on cerebellar relay nuclei and fibers terminating on relay nuclei of somesthetic pathways (Fig. 4). ( I ) Pyramidal axon collaterals terminating on cells of origin of descending bruin stem pathway Thefirst group of fibers comprises collaterals of pyramidal axons which are distributed to cells of origin of other descending fibers, at the cortical, the red nucleus, and the reticular formation level. At the cortical level, according to neuroanatomical (Cajal, 191 1 ; Deschhes et al., 1979b)

339 and electrophysiological (Phillips, 1961 ; Phillips and Porter, 1977) findings in cat and monkey, recurrent collaterals of slow conducting pyramidal tract neurons can convey monosynaptic excitation to fast conducting ones (Phillips, 1961 ;Armstrong, I965 ;Takahashi et al., 1967; Deschcnes et al., 1979a,b). On the other hand, axonal collaterals of fast conducting pyramidal tract neurons can convey disynaptic inhibition, via an interneuron, to slow conducting pyramidal tract neurons (Armstrong, 1965 ; Kameda et al., 1969) and to rubrospinal neurons (Tsukahara et al., 1968; Kelly and Renaud, 1974; Renaud and Kelly, 1974a,b). Moreover, in cat, recurrent collatera!: of pyramidal tract neurons in area 3a can contact cells in area 4 (Zarzecki et al.. 1978) and vice versa (Deschcnes, 1977). At the level of the red nucleus, according to anterograde degeneration findings (in opossum and other marsupials : King et al., 1972 ; Martin and Megirian, 1972 ; in tree shrew : Shriver and Noback, 1967; in cat: Rinvik and Walberg, 1963; Mabuchi and Kusama, 1966; Sadun, 1975; in monkey: Kuypers and Lawrence, 1967; Mabuchi, 1967; i n chimpanzee: Kuypers and Pandya, I 966 ; Petras. 1969 ; in man : Schoen, 1969), anterograde amino acid transport (in rat : Wise and Jones, 1977 ;in cat : Flindt-Egebak, 1979b; in monkey : Hartman-Von Monakow et al., 1979) and retrograde HRP transport findings (Catsman-Berrevoets et a]., 1979) corticorubral projections exist. On the basis of electrophysiological findings in cat (Anderson. 197 1 ; Padel et al., 1973). specific corticorubral fibers (Tsukahara and Kosaka, 1968) may be distinguished in addition to pyramidal tract axon collaterals (in cat: Tsukahara et al., 1968 ; Endo et a l . , 1973; in monkey: Humphrey and Rietz, 1976; Humphrey and Corrie, 1978). Slow conducting pyramidal neurons by means of axon collaterals may convey monosynaptic excitation onto rubrospinal neurons, whereas fast conducting pyramidal neurons may convey disynaptic inhibition (Tsukahara et al., 1968). At the level of the reticular formation, anterograde degeneration (in opossum and other marsupials : Martin et al.. 1975 ; in tree shrew : Shriver and Noback, 1967 ; in rat: Valverde, 1962 : in cat: Kuypers, l958a ; in monkey : Kuypers and Lawrence, 1967) and retrograde HRP transport (Berrevoets and Kuypers, I975 ; Catsman-Berrevoets and Kuypers, 1976) findings have demonstrated the existence of corticoreticular projections which in cat and monkey originate from the motor area. On the basis of electrophysiological findings and retrograde double labeling findings, these projections comprise pyramidal tract axonal collaterals to the mesencephalic (Endo et al., 1973 ; Catsman-Berrevoets and Kuypers, 1981) and medial medullary rcticular formation (Humphrey and Corrie, 1978). Thus through their axonal collaterals, the pyramidal tract neurons can contact cells of origin of other descending pathways, particularly those descending brain stem pathways of the “lateral” (rubrospinal tract) and the “ventromedial” (medial reticulospinal tracts) groups (cf., Kuypers, 1964. 1973). (-7) Py-timidiiI N . W I I i d l i i t ~ ~ r dtermincitiiig s or1 cerebellar reluy nuclei A second gi-oup of cortical projections following the course of the pyramidal pathway tenninates in cerebellar relay nuclei : the olive nuclei, pontine nuclei and lateral reticular nucleus. According to anterograde degeneration (Kuypers, 1958a,b,c ; Sousa-Pinto and Brodal, 1969; cf., Angaut. 1973) and retrograde HRP transport findings (Bishop et al., 1976). pyramidal axon collaterals terminating in the inferior olive have been suspected. Their existence, however. could not be established by electrophysiological techniques (Kitai et al., 1969 ; Miller et al.. 1969 ; cf., Allen and Tsukahara, 1974). Moreover, anterograde degeneration and amino acid transport findings in opossum (Martin et al., 1980) as well as in cat (Saint-Cyr and Courville. 1980) further demonstrate that few cortico-olivary projections exist.

340 They arise mainly from area 6 rather than from area 4 and terminate mainly in the caudal part of the medial accessory olive. At the level of the pontine nuclei, according to anterograde degeneration (in opossum and other marsupials : Harting and Martin, 1970; Martin et al., 197 I , I975 ; Mihailoff and King, 1975; in tree shrew: Shriver and Noback, 1967; in rat: Valverde. 1969: Zimmerman ct al.. 1964; Mihailoff et a]., 1981 ; in cat: Kuypers, 1958a; cf.. Brodal. 1972; in monkey: Kuypers, 1958b ; Kuypers and Lawrence, 1967 ;Dhanarajan et a]., 1977 ;Wiesendanger et al . . 1979 ;Brodal, 1980) and amino acid transport (in rat : Wise and Jones, I977 ;in monkey : Jones and Wise, 1977 ; Wiesendanger et al., 1979) findings, massive cortical projections exist. However, the bulk of these projections seem to be largely independent of the pyramidal tract since in man the number of fibers passing through one medullary pyramid is at least 20 times less than the number of pontine cells (cf., Wiesendanger et al., 1979). Nevetheless, according to electrophysiological findings pyramidal fiber collaterals terminating onto pontocerebellar neurons exist in cat (Endo et al., 1973; Oshima, 1979) as well as in monkey (Ruegg et al., 1977 ; Wiesendanger et al., 1979). According to anterograde degeneration findings (Brodal et al., 1967), cortical projections also reach the lateral reticular nucleus (Kuypers, 1958a; Kunzle and Wiesendanger, 1974). According to electrophysiological findings, however, these corticoreticular projections are only partly composed of pyramidal tract axon collaterals (Briickmoser et al., 1970a,b; Zangger and Wiesendanger, 1973 ; Lundberg , 1979). Thus, corticospinal neurons, by way of axon collaterals can influence cerebrocerebellar loops, via the pontine nuclei and the lateral reticular nucleus. Sensory inputs coming from sensory cortical areas (cf., Allen and Tsukahara, I974 ; Wiesendanger et al., 1979) and from spinal centers (Briickmoser et al., 1970b; Lundberg, 1979) also converge onto these nuclei.

( 3 ) Pyramidal axon collatertils terniinatitig on relay n i d e i of uscetiding spinocortical pathways A third group of cortical projections following the course of the pyramidal pathway terminates on relay cells of ascending somesthetic pathways : the dorsal column nuclei, relaying afferents from the limbs and the ventrobasal complex of the thalamus, relaying lemniscal afferents. According to anterograde degeneration findings (in opossum and other marsupials : Martin et al., 1975 ; in tree shrew: Shriver and Noback, 1967 ; in raccoon: Petras, 1969; in cat and monkey: Chambers and Liu, 1957; Walberg, 1957; Kuypers, 1958a,b; Niimi et al., 1963; Kuypers and Tuerk, 1964; Weisberg and Rustioni, 1979) numerous cortical projections reach the dorsal column nuclei by way of the pyramidal tract. According to retrograde HRP transport findings (in cat: Berrevoets and Kuypers, 1975; Weisberg and Rustioni, 1976; in monkey: Catsman-Berrevoets and Kuypers, 1976; Jones and Wise, 1977 ; Weisberg and Rustioni, 1977) and electrophysiological findings (Gordon and Miller, 1969: Endo et al., 1973; Atkinson et al., 1974 ;Humphrey and Corrie, 1978), however, only a part of these connections is established by corticospinal axon collaterals, which is supported by recent retrograde double labeling findings (Rustioni and Hayes, 198 1). At the level of the ventrobasal complex of the thalamus, relaying lemniscal afferents, anterograde degeneration (Jones and Powell, 1968 ;Rinvik, l968a.b) and amino acid transport (Kiinzle, 1976) findings have shown cortical projections. According to electrophysiological findings (Endo et al., 1973 ; Tsumoto et al., 1975) only a small proportion of these projections are collaterals of pyramidal tract fibers, which is supported by recent retrograde double labeling findings (Catsman-Berrevoets and Kuypers, 198 1).

31 I Thus, by means of their axonal collaterals to different relay nuclei of somesthetic ascending pathways, corticospinal neurons can modulate the sensory information transmitted by these pathways. ( C ) Niirnlx~rriritl rlitrrnrrrr- spcctrirrri of' py'wrnidal fibers

it2

various mamnids

At the level of the medullary pyramid, the fibers are generally gathered into a well localized tract. The counting studies. at this level, made it possible to determine the total number of the pyramidal fibers and to establish their diameter spectrum. In the various species of mammals studied, the total number of fibers contained in one pyramid seems to be related to body weight and brain weight (Towe, 1973b). However. mammals with a corticospinal tract extending throughout the spinal cord (primates. carnivorc5 and rodents) have 4 times as many pyramidal tract fibers for their body weight than those animals with tracts reaching only to the cervical or midthoracic levels (ungulates and marsupials) (Towe. 1973a). These two groups of mammals also differ according to the diameter spectrum of their pyramidal fibers. In the group of mammals in which the corticospinal tract is restricted to the cervical and thoracic cord, the fibers are very thin and have roughly the same diameter, i.e., varying from less than 1 pm up to 2 pin in the tree shrew (Verhaart, 1966). However, in very large animal, such as elephant, the fiber spectrum is also uniform but the fiber diameter is larger (3-5 pni: Verhaart. 1963). In the group of mammals in which the corticospinal tract extends throughout the spinal cord, e.g. carnivores and primates. the fiber spectrum becomes wider and also comprises fibers of larger diameter. In the cat (Van Crevel and Verhaart, 1963a,c), the fiber spectrum extends from less than I pin up to 10 pni. In rhesus monkey, the maximum fiber diameter is around 12 pni, whereas in chimpanzee and man it can reach up to 20 p m (Haggqvist, 1937; Verhaart, 1970b). Thus, the thickest pyramidal fibers occur in those mammals in which direct corticomotoneuronal connections exist. Howevcr. in all species the vast majority of the corticospinal fibers are of small diameter. Thus in the cat 93 %' (N = 80,000) of the fibers measure less than 4 pm and 73 % measure less than 2 pm. Among the fibers with more than 4 pm diameter, only 2 % have a diameter greater than 6 pin (Van Crevel and Verhaart, 1963a). In man, 92% (N = 1,000.000)of the fibers tneasure lcss than 4 pni, and 84% less than 2 p m , whereas only 2.6% have a diameter greater than 6 pm (Lankamp, 1967). The fiber spectrum of the pyramidal tract suggests that in all mammals it is mainly a slow conducting pathway. In higher species, however, a few fast conducting fibers are present, particularly in those species in which direct corticomotoneuronal connections exist.

In the vast majority of the mammalian species the pyramidal tracts decussate in the lower mcdulla oblongata, prior to their descend into the spinal cord. However, in the lower brain stcm no pyramidal fiber decussation exists in the hedgehog (Broere, 1971), the mole (Verhaart, 1967) and the klipdassie (Verhaart, 1967; Broere, 1971). The latter species is considered to be closely related to the elephant (Simpson, 1945), in which only part of the pyramidal tract decussates at the spinomedullary junction (Verhaart, 1963) to form the intercommissural Dexler bundles ( 1907) i n the dorsal part of the ventral funiculi. In all these species, the uncrossed pyramidal fibers descend through the ventral funiculus. In other species, the pyramidal decussation occurs at levels rostra1 to the medullospinal junction. For instance in the

342 echidna (Goldby, 1939; Verhaart, 1970a), a monotreme, it is found at rostral pontine level, and in some chiroptera, such as the bat and flying fox, it is present in the rostral medulla oblongata (Verhaart, 1970a; Broere, 1971). In addition to these interspecies variations in the pyramidal decussation, aberrant pyramidal bundles have been found to occur in individual species and have been most thoroughly studied in man (cf., Nyberg-Hansen and Rinvik, 1963). Thus, in some human cases, corticospinal fibers leave the pyramidal tract at the pontine level and descend lateral to the inferior olive, thus remaining uncrossed when entering the ventrolateral funiculus (Barnes, 1901). Circumolivary pyramidal fascicles may also occur, some of which descend through the ipsilateral ventrolateral spinal funiculus, while the remainder of these circumolivary fibers terminate in the pontobulbar body (Swank, 1934). Frequently. a Pick's bundle exists, composed of recurrent pyramidal fibers which, after passing through the decussation, ascend into the medullary lateral tegmentum. Pick's bundle does not occur only in the human brain but has also been described in mouse, cat and monkey (cf., Valverde, 1966). Crossed pyramidal fibers in the human dorsal funiculus have also been described (Bumke, 1907). Lastly, in some exceptional human cases, the pyramidal decussation has been reported to be lacking altogether (Luhan, 1959 ; Verhaart and Kramer, 1952 ; Verhaart, I970b). ( E ) Spinal funicular trajectory o j cwticmpincil ji'bers

it1 various

tnammals

The spinal funicular trujrctory of the main corticospinal tract (leaving aside the smaller corticospinal tracts that are sometimes present) exhibits considerable variations from one mammalian species to another. These variations can probably be attributed to the fact that the pyramidal tract is phylogenetically young, since older tracts present a relatively more constant pattern (Nyberg-Hansen and Rinvik, 1963 ; Noback and Shriver, 1966). In the order of marsupials, most of the corticospinal fibers are found in the ventral part of the dorsal funiculus. This is true for both the polyprotodont (North American opossum: Bautista and Matzke, 1965; Martin and Fisher, 1968) and diprotodont varieties (quokka wallaby: Watson, 1971a ; kangaroo : Watson, 1971b ; Tasmanian brush-tailed possum : Martin et al., 1970; Rees and Hore, 1970; Tasmanian potoroo: Martin et al., 1972). In this respect it is of importance to emphasize that the location of the main corticospinal tract, however, does not seem to be consistent throughout a given order of mammals (Jane et a]., 1965). For example, in some insectivores, such as the hedgehog and mole (Broere, 1971), the bulk of the pyramidal fibers descend uncrossed through the ventral funiculus, whereas in the tree shrew, the pyramidal fibers descend via the dorsal funiculus (Jane et al., 1965; Verhaart, 1966; Shriver and Noback, 1967). Therefore the tree shrew was moved from its position in the order of insectivores (Weber, 1928) either to a primitive position in the order of primates (Le Gros Clark, 1934; Simpson. 1945; Fiedler, 1956: Broers, 1963, 1964) o r to a separate position (Shriver and Noback, 1967). In several rodents, e.g. the rat (Goodman et al., 1966; Brown, 1971 ; Donatelle, 1977), coypura (Goldby and Kacker, 1963) and capybara (Broere, 1971), the bulk of the pyramidal fibers also descends through the dorsal funiculus. However, in the rabbit, the pyramidal fibers descend mainly through the lateral funiculus (Douglas and Barr, 1950; Haarsten, 1962). Therefore, the rabbit was moved from its position in the order of rodents to a separate order of Lagomorphae (Douglas and Barr, 1950). Finally, the corticospinal fibers can descend through more than one funiculus. In the armadillo, corticospinal fibers cross and descend in the dorsal portion of the ventral funiculus as well as in the lateral funiculus (Doni et al., 1971). In carnivores such as cat (Chambers and Liu, 1957; Nyberg-Hansen and Brodal, 1963;

343 Armand and Kuypers, 1980), dog and raccoon (Buxton and Goodman, 1967), the main corticospinal tract invariably descends through the dorsolateral funiculus. The same is true in primates both i n prosimians, such as the slow loris and galago, and in simians, such as the callitrichidae (marmoset), cebidae (Snimiri), cercopithecidae (Mucacci), hylobatidae (hylobates). pongidae (chimpanzee) and nian (Verhaart, 1970b). However, in many species subsidiary funicular trajectories are also present. Hence, in several individual species, 4 different corticospinal tracts can be encountered: a main crossed dorsolateral tract and an uncrossed dorsolateral tract as well as a crossed and an uncrossed ventral tract. Anterograde degeneration findings in Marchi (Manghi, 1956, 1958; Glees, 1961) and in silver impregnation material (Walberg and Brodal, l953 ; Kuypers, 1958a; Niimi et al., 1963 ; Nyberg-Hansen and Brodal. 1963) indicate that these 4 types of funicular trajectories exist in the cat. According to retrograde HRP transport findings, 92 O/c of the dorsolateral corticospinal fibers at C G C 7 are crossed and 8 ‘2 uncrossed, whereas 63 o/c of the ventral corticospinal fibers are crossed and 37 % uncrossed (Armand and Kuypers, 1980). ( F ) Ro.~troc~tiictlol r ~ . ~ t ~tint1 i i t tormincitioti circa of corticospinal fibers in vcrrious mamrtiuls. The ro.strocricrrki1 o.Y~(w/ of the corticospinal fibers and their terrnitmtion ureu in the spinal grey matter vary among different species of mammals. Thus, from one species to the other, the corticospinal terniination area progressively enlarges, such that, in addition to the dorsal horn. it comprises the intermediate zone, and in some species also the ventral horn including the motoneuronal cell groups. For practical purposes. mammals can therefore be divided into 4 groups (Kuypers. I98 I ). based on the rostrocaudal extent of the corticospinal tract and the distribution of the corticospinal fibers in the spinal grey matter.

( I ) Mrrrntiicrls uYth c~or.tic.os~~iiiul fi1~rr.sr.rtetiding only to cervical or mid-thoracic segments uirtl toriniii(itiiig in the rlorsrrl horri In thisfi‘rst groz4p oJ’inc~intntil.s, the main corticospinal tract extends as far as the cervical or mid-thoracic level, whereas the minor tracts that are sometimes present, generally reach only the cervical level. However, even for the main corticospinal tract, most of the terminations are concentrated in the cervical enlargement (C5-C8). According to anterograde degeneration findings, these corticospinal fibers generally terminate contralaterally, chiefly in the dorsal horn (lamina IV and the medial parts of laminae V and VI, according to Rexed (Rexed, 1952, 1954 ; Martin and Fisher, 1968)).They terminate to a lesser extent in the most dorsolateral parts of the intermediate zone (lateral parts of laminae V and VI) and in some species in lamina VII. In most of these species, some ipsilateral corticospinal terminations may also occur in the same spinal areas. The species presenting this “primitive” pattern of corticospinal terminations include the goat (Haarsten and Verhaart. 1967), elephant (Verhaart, 1963), rabbit (Haarsten. 1962). tree shrew (Jane et al., 1965; Verhaart, 1966; Shriver and Noback, 1967). sloth (Strominger, 1969) and armadillo (Dom et al., 1971) (Fig. 5 ) . In the order of marsupials. a progressive ventral expansion of corticospinal terminations within the spinal grey matter occurs. Thus in polyprotodont marsupials such as the kangaroo (Watson. 197 I b) and the North American opossum (Bautista and Matzke, 1965 : Martin and Fisher, 1 968). according to anterograde degeneration findings, the corticospinal fibers reach no further caudally than segment T5. The terminal area within the spinal grey matter, in both species. is mainly concentrated in the mcdial part of the dorsal horn (medial parts of laminae Ill-VI). In dip-otodont marsupials, such as the quokka wallaby (Watson, 197 la), Tasmanian potoroo (Martin et al., 1972) and Tasmanian brush-tailed possum (Martin et al., 1970: Rees

344

CERV.

THOR.

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z

;

\

; \-\-:-:*

Pz

;

: z

i \

P;

; b

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b

b

bb

i

': z:

;:

\:-

bs

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LUMB.

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Fig. 5 . Mammals with corticospinal fibers only in cervical or midthoracic segments and terminating mainly in the dorsal horn. The symbols of the different lines refer to laminae IV-VI (hatched). lamina VII (dots), lamina VIII (hatched with lines in the opposite direction) of the inset diagram of the spinal cord (modified from Kuypers, I98 I ) .

and Hore, 1970), the corticospinal fibers extend more caudally, reaching at least the T7, T I 2 and T10 segment, respectively. In these 3 species, as in polyprotodont marsupials, the major area of termination is the medial part of the dorsal horn. However, in the Tasmanian potoroo and the Tasmanian brush-tailed possum, a few fibers terminate in lamina VII. Moreover, in the Tasmanian brush-tailed possum, the corticospinal termination area spreads over the lateral parts of laminae IV, V. VI and VII (Martin et al., 1970) and possibly also over the medial part of laminae VIll (Rees and Hore, 1970). Thus, in these species many of the fibers ramifying within lamina VII are in close proximity to motoneurons of lamina 1X. This close proximity between some corticospinal fibers and ventral horn motoneurons in the Tasmanian brush-tailed possum has been emphasized by clectrophysiological findings (Hore and Porter, 197 I ) . Nevertheless, n o corticospinal termination has been found within lamina IX (Martin et al., 1970). The progressive caudal extent and ventrolateral expansion of the corticospinal terminations in the spinal grey matter of polyprotodont and diprotodont marsupials may be related to the increasing motor capacities in this group of species. For example in contrast to the North American opossum, the Tasmanian potoroo is capable of moving rapidly on the ground by hopping on its hindlimbs, and of grasping food with its forepaws, although these are mainly used for digging (Martin et al., 1972). Another contrast is provided by the considerable prehensile ability of the extremities of the arboreal Tasmanian brush-tailed possum when climbing and grasping food (Martin et al., 1970; Rees and Hore, 1970). Nevertheless, neither the Tasmanian potoroo nor the brush-tailed possum possess the ability to move the digits

345

individually (Rees and Hore. 1970; Martin et al., 1972) which is in keeping with the lack of corticospinal termination within lamina IX . In spite of these significant differences between the various species of marsupials, all of them have in common a restricted caudal extent of the corticospinal fibers leading to the cervical enlargement. In these animals the cerebral cortical influence on the lumbosacral enlargement therefore must depend on a polysynaptic excitation either by way of descending brain stem pathways (Martin and Doni, 1970) or by way of propriospinal neurons connecting the cervical or thoracic to the lumbosacral cord (Martin et al., 1970). In addition, in all marsupials at the segmental level the bulk of the corticospinal fibers terminate in the medial part of the dorsal horn (laminae IV--VI). This dorsal distribution suggests that one of the main functions of the corticospinal tracts in marsupials is to modulate incoming sensory information (Martin et al., 1972). However, these tracts may also indirectly influence the ventral horn motoneurons through internuncial connections. This generally unifomi mode of corticospinal terminations in the dorsal grey matter at the segmental level in tiiarsupials may be related to the fact that at the cortical level these fibers are derived from a granular “sensorimotor amalgam” containing both sensory and motor representation (Lende, 1969 ; Martinet al., 1970). However, at this cortical level, some variations also occur. According to anterograde degeneration findings in the Tasmanian potoroo (Martin et a l . , 1972). the parietal cortex projects mainly to laminae 111 and IV, whereas the cortex directly caudal to the orbital sulcus projects mainly to the medial parts of laminae V and VI. The caudal extent and termination area of the corticospinal fibers of metatherian mammals are less developped than i n eutherian mammals. However, the gradient of extension of the corticospinal tcrminations in these two orders of mammals are comparable. These parallel variations (Noback and Shriver, 1966) could be of interest if it were established that metatherian and eutherian mammals appeared simultaneously from a common therian trunk at the end of the inferior cretaceous era (Hoffstetter, 1970).

( 2 ) M~irriinulstt’ith c~ortic~os~r,inulfihrrs c).rtentling throughout the spinal cord und terrnirzating itr the dorsal horri u i i d the iritertneditrtc, , - o i i c ~ In asecondgroiip c~f’mrrmnirils,the corticospinal fibers extend throughout the spinal cord. In these animals the corticospinal termination area comprises the dorsal horn and the lateral and medial parts of the intermediate zone. Representative species of this second group are procavia (Verhaart, 1067), cat (Chambers and Liu, 1957; Kuypers, 19.58~;Niimi et al., 1963; Nyberg-Hansen and Brodal, 1963 ; Kostyuk et al., 1973 ; Hanaway and Smith, 1978 ; FlindtEgeback. 1979a), dog (Buxton and Goodman, 1967), marmoset (Shriver and Matzke, 1965) and rat (Brown, 1971: Donatelle, 1977) (Fig. 6). According to anterograde degeneration findings in cat (Niimi et al., 1963 ; Nyberg-Hansen and Brodal, 1963) crossed dorsolateral corticospinal fibers enter the spinal grey matter through the lateral aspect of laminae V and VI, and spread in a fan-shaped fashion over laminae IV-VII. Among these fibers two components can be distinguished : a dorsomedial component terminating in laminae IV, V and the dorsomedial part of IaminaVI (Szentagothai. 1964); and a ventroinedial component terminating in the remainder of lamina VI and the dorsal part of lamina VII. The few uncrossed fibers (8%) (Armand and Kuypers, 1980) in the dorsolateral funiculus (Walberg and Brodal, 1953; Manghi, 1956; Glees, 1961 ; Nyberg-Hansen and Brodal, 1963) terminate in the same area on the ipsilateral side. The crossed (63%) and uncrossed (37 c/o ventral corticospinal fibers (Armand and Kuypers, 1980) enter the spinal grey matter from the ventral funiculus by way of the most medial portion of lamina VII. Their terminations are difficult to distinguish from those of the dorsolateral corticospinal fibers. In

346 cat

dog

procavia

rai

Fig. 6. Mammals with corticospinal fibers extending throughout the spinal cord and terminating in the dorsal horn and the intermediate zone. The symbols of the different lines refer to laminae IV-VI (hatched), lamina VII (dots), lamina VTII (hatched with lines in the opposite direction), dorsolateral motoneuronal cell groups of lamina IX (black stars) of the inset diagram of the spinal cord (modified from Kuypers, 1981).

view of anterograde degeneration (Nyberg-Hansen and Brodal, 1963) and amino acid transport findings (Flindt-Egebak, 1979a), they probably terminate bilaterally, mainly in the transitional area between laminae VII and VIII. However, in the cat, practically no corticospinal fibers terminate in lamina VIII (Nyberg-Hansen and Brodal, 1963 ; Flindt-Egebak, 1979a) and none enter the lateral motoneuronal cell groups of lamina IX (Szentagothai-Schimert, 1941 ; Walberg and Brodal, 1953; Chambers andLiu, 1957; Kuypers, 1 9 5 8 ~Niimiet ; al., 1963). In contrast, in the dog, another carnivore, many corticospinal fibers terminate in lamina VIII, but mainly in the cervical cord. However, as in cat no cortical fibers are distributed to the motoneuronal cell groups (Buxton and Goodman, 1967). Yet, according to electrophysiological findings (Elger et al., 1977) in the rat, monosynaptic corticomotoneuronal connections exist mainly in the cervical enlargement (Janzen et al., 1977). The two components involved in the intraspinal distribution of corticospinal terminations in this second group of mammals are derived from different cortical areas. Thus, according to anterograde degeneration findings in cat, the primary (Nyberg-Hansen and Brodal, 1963) and secondary (Chambers and Liu, 1957) somatosensory cortex distribute fibers mainly to the dorsomedial parts of the spinal grey, i.e., lamina IV and the medial part of laminae V and VI. Moreover, according to retrograde HRP transport findings, the corticospinal fibers arising in the primary and secondary somatosensory cortex (Biedenbach and Devito, 1981) are mainly

347 crossed and descend through the dorsolateral funiculus (Armand and Kuypers, 1980). In contrast. the primary motor cortex mainly distributes fibers to laminae V-VII (Nyberg-Hansen and Brodal. 1963). These latter corticospinal fibers are of 4 types: crossed and uncrossed, descending through either the dorsolateral or the ventral funiculus (Armand and Kuypers, 1980). This differential distribution of corticospinal fibers in respect of their cortical area of origin. however, is not absolute, for both the primary somatosensory and the primary motor cortex project to lamina V and the dorsomedial part of lamina VI (Nyberg-Hansen and Brodal, 1963). Within the primary motor cortex (cytoarchitectonic area 4) (Hassler and Miihs-Clement, 1964) corticospinal fibers have a differential origin in respect of their segmental termination (Fig. 7). According to retrograde HRP transport findings two portions of area 4, located medially and laterally in the pericruciate cortex, generate mainly crossed corticospinal fibers which descend through the dorsolateral funiculus (Armand and Kuypers, 1980) and are distributed to the cervical and lumbosacral enlargements (Armand, 1978), respectively. These two portions of area 4 will be referred to as the "specific" zones. The remaining central portion of area 4, on the other hand, generates both crossed and uncrossed fibers which descend through the dorsolateral and ventral funiculi (Armand and Kuypers, 1980). Antidromic stimulation (Armand et al., 1974) and retrograde HRP transport (Armand and Aurenty, 1977 ; Gross et al.. 1978) findings have shown that within this central portion of area 4 there exists a "common" corticospinal zone which projects to both the cervical and lumbosacral enlargements. Thus. there exists in this area a population of corticospinal neurons which terminate individually or as a group i n both spinal enlargements. Anterograde degeneration findings suggested the possible existence of spinal branching of

B

C

Fig. 7. Synthetic diagram ot'the various corticospinal projections originating in different parts of area 4 in the cat. A : specific crosscd corticospinal projections for the cervical (C) or lumbosacral (L) enlargement, via the dorsolateral funiculus. B : specific bilarerlil projections for one enlargement, via the dorsolateral and ventral funiculi. C : common biherlil corticospinal projections to both cnlargenients, via the dorsolateral and ventral funiculi.

348 corticospinal axons (Tyner, 1974). Intra-axonal injection of HRP has further shown the existence of spinal collaterals of corticospinal neurons in cat (Futami et al., 1979). This is in keeping with earlier electrophysiological findings (Shinoda et al., 1976; Shinoda, 1978 ; Shinoda and Yamaguchi, 1978). According to these findings in cat all (N = 30) the corticospinal neurons which project from the “specific” forelimb area to the cervical cord give off from 3 to 7 collaterals to the intermediate zone of the cervical enlargement (Shinoda and Yamaguchi, 1978). Among these “specific” corticospinal neurons 57 92 are fast and 43 % are slow conducting. In addition, 6 % of the corticospinal neurons, which give off one cervical collateral, have their stem-axon terminating in the lumbosacral enlargement (Shinoda et a]., 1976). These “common” corticospinal neurons which project to both enlargements include fast conducting neurons. In a recent double retrograde tracer study, HRP and tritiated enzymatically inactive HRP ([3H]apo-HRP; Hayes and Rustioni, 1981) were injected in the spinal grey matter of the cervical and the lumbosacral enlargement respectively. “Specific” corticospinal neurons, projecting to only one spinal enlargement, were thus labeled by only one marker, whereas “common” corticospinal neurons giving off axon collaterals to both spinal enlargements were double labeled. Within area 4 , the “specific” corticospinal neurons projecting to either the cervical or the lumbosacral enlargement were concentrated in the two “specific” zones. In the middle part of area 4, corticospinal neurons projecting to the lumbosacral enlargement were intermingled with others projecting to the cervical one. Within this “common” zone also a few double labeled neurons were observed which distribute collaterals to both the cervical and the lumbosacral enlargements.

(3) Mammals with corticospitialfihers extending throughout the spinal cord und terminating in dorsal horn, intermediute zone, and dorsolateral purts of the Iuterul motoneuronal cell groups In a third group of mammuls, corticospinal fibers also extend throughout the spinal cord and also terminate in the dorsal horn and the intermediate zone. However, in this third group many corticospinal fibers are also distributed to the ventromedial parts of the ventral horn (lamina VIII) bilaterally and some are distributed to the dorsolateral motoneurons. This group of mammals comprises many anthropoid simians (Fig. 8). However, two species of carnivores, i.e., the racoon and the kinkajou, also belong to this group (Petras and Lehman, 1966; Buxton and Goodman. 1967 ;Wirth et al., 1974). The contralateral distribution of cortical fibers to the dorsolateral motoneuronal cell groups, in this third group of species, is probably related to their capacities to execute relatively independent finger movements. This would be in keeping with the striking digital ability of the forepaw in the racoon, which ability is lacking in cat and dog, two other carnivores. The prosimian slow loris (Campbell et al., 1966) and galago (Goode and Haines, 1975) may be included in this group. In these animals corticospinal terminations are also abundant in the ventromedial parts of the ventral horn on both sides along the whole spinal cord. In addition, some corticospinal fibers, although not approaching the motoneuronal cell bodies, are present well within the area occupied by the dendritic arbors of the motoneurons in the dorsolateral part of the ventral horn (Goode and Haines, 1975). Among the anthropoid simians, New World (capuchin, spider, woolly and saimiri) and Old World (rhesus and vervet) monkeys exhibit the general pattern of corticospinal terminations typical of this third group of mammals (Liu and Chambers, 1964; Petras, 1968 ; Harting and Noback, 1970; Tigges et al., 1979). Thus, in the rhesus monkey, according to anterograde degeneration findings (Kuypers, 1958c, 1960b), two groups of corticospinal fibers can be distinguished. The first group terminates contralaterally in the internal basilar region of the

raccoon

slow

loris

galago

rhesus

Fig. 8 . Mammals uith extcnsive corticospinal fibers terminating in the dorsal horn, the intermediate zone and tlorsolateral motoneuronal cell groups. For symbols see Fig. 6 (modified from Kuypers, 198 I ) .

dorsal horn and its nucleus proprius, whereas the second group terminates mainly contralaterally in the external basilar region of the dorsal horn, the dorsolateral part of the intermediate zone, and bilaterally in its ventromedial part. In addition, corticospinal terminations are present contralaterally in the dorsolateral motoneuronal cell group (Kuypers, 1960a; Liu and Chambers, 1964). However, according to anterograde degeneration findings (Liu and Chambers, 1964 ; Petras, 1969) and electrophysiological findings (Bernhard and Bohm, 1954). some corticospinal fibers may also terminate bilaterally within the ventromedial motoneuronal cell group. The two groups of corticospinal fibers in the rhesus monkey, which terminate in the dorsal horn and in the intermediate zone, as well as the motoneuronal cell groups are derived from different cortical areas in the same way as observed in the cat. Thus, according to anterograde degeneration (Kuypers, 1958c, 1960b) and amino acid transport (Coulter and Jones, 1977) findings, the first group is mainly derived from the postcentral primary somatosensory cortex (areas 3b, 1,2 and S), whereas the second group is mainly derived from the precentral primary motor cortex and area 3a, a transitional area within the central sulcus. Moreover, within the precentral gyms, different types of corticospinal projections exist (Kuypers and Brinkman? 1970). A lateral and medial area along the central sulcus mainly generates corticospinal projections terminating in the contralateral dorsolateral part of the intermediate zone, in the cervical and lumbosacral enlargement respectively. In addition, these two separate areas

350 distribute fibers to the adjoining contralateral dorsolaterdl motoneuronal cell groups of one or the other enlargement. In contrast, the intervening area along the central sulcus and the rostral parts of the precentral gyrus distribute fibers along the whole length of the spinal cord, again contralaterally, to the dorsolateral part of the intermediate zone and bilaterally to the ventromedial part of the intermediate zone. Moreover, according to retrograde HRP transport findings, the rostral part of MI and the caudal part of S1 represent “common zones” for both enlargements, containing neurons retrogradely labeled after both cervical and lumbar HRP injections (Murray and Coulter, 1981). In the rhesus monkey as in the cat, spinal branching of corticospinal axons has been demonstrated by electrophysiological findings in acute (Asanuma et al., 1979; Shinoda et al., 1979) and chronic (Fetz et al., 1976; Fetz and Cheney, 1978) experiments. Thus “specific” corticospinal neurons distribute collaterals to different segments of one spinal enlargement, either the cervical (Shinoda et al., 1979) or the lumbosacral one (Asanuma et al., 1979). According to the electrophysiological findings in acute experiments (Shinoda et al., 1979), these collaterals may terminate in the intermediate zone of several segments of one spinal enlargement and may also terminate within one or more than one motor nuclei (Asanuma et al., 1979; Shinoda et al., 1979, 1981). Correspondingly, electrophysiological findings in chronic experiments indicated that 213 of the precentral neurons ( N = 2 16) which establish corticomotoneuronal connections have a “muscular field” of more than one muscle (Fetz and Cheney, 1978). The remaining 113 on the other hand have a “muscular field” restricted to one muscle (Fetz and Cheney, 1978). This is supported by electrophysiological findings in acute experiments (Shinoda et al., 1979). These “specific” corticospinal neurons are all fast conducting (Fetz et al., 1976; Asanuma et al., 1979; Shinoda et al., 1979). The ventral expansion of the corticospinal termination area in this third group of mammals as compared with the second one thus includes the ventromedial part of the intermediate zone, bilaterally, as well as the dorsolateral motoneuronal cell group contralaterally. This is in keeping with the advanced motor capacities of this group as exemplified by the capacity of the rhesus monkey to execute individual finger movements. The carnivores racoon and kinkajou and the simians as well as the prosimians are plantigrade in posture and gait and generally possess hairless palms and soles and pentadactylous limbs (Schultz, 1968; Petras, 1969). The prosimians in which the corticospinal fibers do not approach the cell bodies of the motoneurons have a stereotyped prehensive pattern in which no distinction is made between “power” and “precision” (Bishop, 1964). In simians, in which corticospinal fibers are distributed throughout the dorsolateral motoneuronal cell group, “precision” becomes possible through the ability to move the index finger independently and the opposability of the thumb (pseudoopposability, in New World monkeys; Phillips, 197 1) allowing precision grip between thumb and index finger (Napier, 1961). In this context, it is of interest to compare the moderate number of corticospinal terminations among the coccygeal motoneurons innervating the tail of rhesus, vervet and capuchin monkeys, with the abundance of bilateral terminations in spider and woolly monkeys (Petras, 1968; Tigges et al., 1979), which have “glabrous-tipped precision-gripping tails” (Phillips, 1971).

( 4 ) Mammals with corticospirza1,fihrrs extending throughout the spinal cord and terminating in dorsal horn, intermediate zone, und dorsolnterul US ell as ventromediul parts of the lateral motoneurorial cell groups In this fourth group oj”mammals , corticospinal fibers also extend along the length of the spinal cord, and also terminate in the dorsal horn, the intermediate zone and the lateral motoneuronal cell group. However, the corticospinal fibers in this group are distributed more

chimpanzee

&

man

Fig. 9. Mainm;ils with extc‘nsivc‘ corticospiniil I‘ihers terminating in the dorsal horn, the intenmediate zone and dorsolateral (b1;ic.k \tars) and ventroinedial (white stars) niotoneuronal cell groups (modified from Kuypers, 198 I ).

profusely to motoneurons than in the preceding group and are distributed not only to motoneurons of distal extremity muscles as in the rhesus monkey, but also to motoneurons of girdle and proximal extremity muscles. This pronounced ventral expansion of the corticospinal fiber termination area may be accompanied by a less dense projection to the dorsal horn in the chimpanzee (Kuypers, 1964)and man (Schoen, 1964).Representative species of this group of highest primates are the gibbon (Petras, 1968),chimpanzee (Kuypers, I964 ;Petras, 1968)and man (Schocn. 1964. 1969) (Fig. 9). In the 4 groups of mammals examined, the cortical fibers thus exhibit an increasingly caudal distribution in the spinal cord and their terminations in the spinal grey enlarged progressively from the dorsal horn, through the inteimediate zone, to the lateral and medial part of the ventral horn. However. several species occupied intermediate positions with respect to these 4 groups. It is therefore proposed that in regard of the organization of the corticospinal connections, each living species represents a compromise between a certain degree of development along the gradient described and a behavioral adaptation to its environment. From the present survey the following conclusions may be drawn. In their “primitive” form, the corticospinal terminations in the dorsal horn may subserve mainly a cortical modulation of the incoming sensory information at the spinal level. This cortical modulation is also possible at supraspinal level, by way o f the corticospinal axon collaterals to relay nuclei of ascending pathways. In their most “highly evolved” forms, the corticospinal terminations in

352

the ventral horn establish monosynaptic connections with motoneurons of distal and proximal extremity muscles. These corticomotoneuronal connections probably provide the capacity to execute highly fractionated movements. However, in most of the species the corticospinal terminations display a distribution between these two extreme patterns and are most abundant in the intermediate zone, where they influence mainly the internuncial circuits. ACKNOWLEDGEMENTS 1 am grateful to Professor H.G.J.M. Kuypers and Doctor J. Massion for their encouragements during this work. This study was supported by Grants C.R.L. 79.4.337.6. INT of the INSERM (Institut National de la SantC et de la Recherche Medicale) and ETP/TW/ I52 1 of the European Science Foundation (European Training Program in Brain and Behaviour Research). REFERENCES Allen, G.I. and Tsukahara, N. (1974) Cerebrocerebellar communication systems. Physiol. Rev.. 54: 957-1006. Anderson, M.E. (1971) Cerebellar and cerebral inputs to physiologically identified efferent cell groups in the red nucleus of the cat. Brui~iRes., 30: 49-66. Angaut, P. ( 1973) Bases anatomo-fonctionnelles des interrelations cerebello-cCrebrales. J . Physiol. (Puris), 67 : 53A-116A. Aretaeus (1856) The exfcint works ofArercieus. The Sydenham Society, London, 1856 (cf. Thomas, 1910). Armand, J. (1978) Topical versus diffuse organization of the corticospinal tract in the cat. I n : Svmposiutn on Pyramidal Microconnexions crnd Motor Control. Marseille. July 1977, J. Massion, J . Paillard and M. Wiesendanger (Eds.). J . Physiol. (Pcrris). 74: 227-230. Armand, J. and Aurenty, R. (1977) Dual organization ofmotorcorticospinal tract in the cat. Neurosci. L u f f . ,6: 1-7. Armand, J. and Kuypers, H.G.J.M. (1980) Cells of origin of crossed and uncrossed corticospinal fibers in the cat. A quantitative horseradish peroxidase study. Exp. Brcrin Res., 40: 23-34. Armand, J., Padel. Y. and Smith, A.M. (1974) Somatotopic organization of the corticospinal tract in cat motorcortex. Bruin Rus., 74: 209-227. Armstrong, D.M. (1965) Synaptic excitation and inhibition of Betz cells by antidromic pyramidal volleys. J . Physiol. (Lond.), 178: 37-38P. Asanuma, H . , Zarzecki, P., Jankowska, E . , Hongo, T. andMarcus. S. (1979) Projection o f individual pyramidal tract neurons to lumbar motor nuclei of the monkey. E.vp. Brcrin Rrs.. 34: 73-89. Atkinson, D.H., Seguin, J.J. and Wiesendanger, M. (1974) Organization of corticofugal neurones in somatosensory area 11 of the cat. J . Physiol. (Lond.). 236: 6 6 3 4 7 9 . Bagley, C. (1922) Cortical motor mechanism of the sheep brain. Arch. Neurol. Phychicit. (Chic.), 7 : 4 1 7 4 5 3 . Ballet, G. et Faure, M. ( I 899) Atrophic des grandes cellules pyramidales dans la zone motrice de I'Ccorce cerebrale, aprks la section exPCrimentale des fibres de projection, chez le chien. Rev. ncurol., 7 : 4 2 6 4 2 7 . Barnes, S . (1901)Degeneration in hemiplegia: with special reference to a ventrolateral pyramidal tract, the accessory fillet and Pick's bundle. Rrciin. 24: 463-501. Barron, K.D. and Dentinger, M.P. (1979) Cytologic observations on axotomized feline Betz cells. I. Qualitative electron microscopic findings. J . Neuropcith. c.rp. Neurol.. 38: 128-1 5 1 . Bautista, N.S. and Matzke, H.A. ( I 965) A degeneration study of the course and extent o f the pyramidal tract of the opossum. J . romp. Neurol., 124: 367-376. Bernhard, C.G. and Biihm, E. ( 1954) Cortical representation and functional significance of the corticomotoneuronal system. Arch. Nuurol. Psychiut. ( C h i c . ) , 72: 473-502. Bcrrcvoets. C.E. and Kuypcrs. H.G.J.M. ( 1975) Pericruciate cortical neurons projecting to brain stem reticular formation, dorsal column nuclei and spinal cord in the cat. Nrurosci. Left., 1 : 257-262. Biedenbach, M.A. and Devito, J.L. ( 1980) Origin of the pyramidal tract determined with horseradish peroxidase. Bruin Res., 193: 1-17. Bishop, A. (1964) Use of the hand in lower primates. I n : Evolufioncrry trnd Genetic Biology cffrimures. V o / . 2. J. Buettner-Janusch (Ed.), Academic Press, New York. pp. 133-225. Bishop,G.A.. McRea, R.R. andKitai, S.T. (1976) A horseradishperoxidase studyofthecortico-ohvary projection in the cat. Bruin Res., 1 I6 : 3 0 6 3 1 1.

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