Ascending projections of the medial cerebellar (fastigial) nucleus: An experimental study in the cat

49

BRAIN RESEARCH

A S C E N D I N G PROJECTIONS OF T H E MEDIAL CEREBELLAR (FASTIGIAL) NUCLEUS: AN E X P E R I M E N T A L STUDY IN T H E CAT

PIERRE A N G A U T AND DAVID BOWSHER

taboratoire de Neuraphysiologie Gdndrale, Coll~ge de France, Paris 16e (France) and Laboratory (~f Nenrobialo.gy. Department of Anatomy, University of Liverpool, Liverpool (Great Britain) (Accepted May 25th, 1970)

INTRODUCTION

The medial (fastigial) nucleus of the cerebellum is best known as the source of cerebellar efferents to the lower brain stem (see particularly Thomas et al.3~). Proiections to the vestibular nuclei have recently been subjected to detailed study by Walberg et al. 36. On the other hand, the literature contains very much less information on 'ascending' piojections from the medial nucleus. Although there is no disagreement on the existence of ascending projections, the regions of the nucleus giving rise to them are still disputed. Voogd 34 speaks of an uncrossed component arising from the rostral part of the nucleus, and this possibility is not eliminated by Thomas et al. 31. Jansen and Jansen iv, on the contrary, ma;ntain not only that ascending fibres arise only from the caudal half of the nucleus, but that they decussate within the cerebellum. All authors agree that ascending fastigiofugal fibres leave the cerebellum by way of the superior cerebell~r peduncle, but there is some disagreement in the literature on the course of these fibres. Probst z2 describes a dorsal trajectory distinct from that of the brachium conjunctivum, whereas Jansen and Jansen 17, on the basis of retrograde degeneration, consider fastigiofugal fibres to be present within the brachium conjunctivum contralateral to the side of origin. Voogd 34 does not reject the idea of a contingent in the ipsilateral brachium conjunctivum. A large measure of confusion reigns in the literature concerning the terminations of ascending fastigiofugal fibres. It has been maintained 24 that no fibres go beyond the midbrain reticular formation; Probst 22, in one of the most precise early studies on the question, stated that the lowest site of termination is in the region of the posterior commissure, and tbis has been confirmed by many more recent investigations, while further rostrally zones of termination occur within the thalamus. At this level, most authors consider the principal end-station to be the centrum medianum (CM) (see Thomas et al.31); in addition, a projection has also been recognized in the ventraJ region of the thalamus, in what appears to be the nucleus ventralis lateralis (VL). But in fact none of the earlier investigations gives very precise details Brain Research, 24 (1970) 49-68

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P. ANGAUT AND D: BOWSHER

on the thalamic region concerned. Consequently no opinion is to be found on the organization of these projections, such as has been elucidated for the fastigio-vestibular projections 36,z7. The present investigation has been undertaken to gain a clearer idea of the origin, course, and above all the mesencephatic and thalamic distributions of ascending fastigial efferents. Probable functional correlates may be adduced from the findings to be presented. MATERIAL AND METHODS

Eight adult cats. weighing between 2 and 3 kg, were used. Anaesthesia was obtained by the intraperitoneal administration of Nembutal. After the cats had been fixed in a stereotaxic apparatus, small craniectomies were performed under aseptic conditions with a dental drill to allow an oblique approach by the coagulating electrode, so as to avoid the bony tentormm cerebelli. Bipolar concentric steel electrodes were used having an external diameter not greater than 0.7 ram. tip diameter 30-50 #m, interpolar distance of about 1 mm. and resistance of 50-70 k~2. The stereotaxic coordinates of the medial nucleus showed considerable variation, and for this reason physiological recording criteria were used, i.e. the fact that spontaneous activity within the nucleus is easily recognized from that of the white matter passed through in the course of the descent of the electrode. When the accurate placement of the tip was recognized, the coagulation was performed with the same electrode. Destruction of the nucleus, in whole or in part, was then carried out by passing a direct current of 2-3 mA for 5-10 sec, either through both poles of the electrode. or through the inner pole and an indifferent electrode attached to the skin. After survival periods varying from 4 to l0 days, the animals were killed bv intracarotid or intracardiac perfusion of 10~,~ formol under barbiturate anaesthesia. The brains were removed into fixative and preserved for 10 days to 4 months before histology was undertaken. At this stage, the cerebellum was removed from the brain stem by transection of the peduncles. Most of the cerebella were cut transversely in serial frozen sections at 00 #m. and stained by the method of Nissl. The sections were placed in an enlarging projector, and traced at a magnification of about 10 1,. This procedure allowed accurate outlining of lesions and nuclear contours. In a small number of cases, the cerebellum was serially sectioned horizontally at 15 u m . One section in 15 was then stained by the Nissl method and an adjacent one was impregnated by the Nauta 21 technique. In this way, it was possible to observe, in addition to the extent of the lesion, the intracerebellar course of degenerating fibres. In most cases the brain stem (including diencephalon) was cut in serial coronal frozen sections at 15 # m ; one section in 15 was impregnated by the method of N a u t a and an adjacent one was Nissl-stained. In a few experiments the brain stem was cut horizontally. Projection drawings of sections were made as described above; degeneration was interpreted according to the usual criteria 6. Before we describe our experiments, it is necessary to give a precise description Brain Research, 24 (1970) 49-68

ASCENDING FASTIGIAL PROJECTIONS

51

of the thalamic area involving and surrounding the VL, as much confusion has reigned in the literature concerning the delineation and nomenclature of the various nuclei concerned. One of us has recently discussed the pointL The nomenclature here employed is that used by Jasper and Ajmone Marsan 18. Rinvik 25 re-evaluated on a cytoarchitectonic basis the delineation of these nuclei in the cat. For the most part we agree with his description of the VL. Suffice it here to discuss a few particulars. We have observed that the medialmost part of the VL, apposed to the internal medullary lamina, shows a lower cell density than more lateral regions, while it seems passed through by more numerous fibres. Thus, this medial nuclear strip has a paler appearance than the more lateral part of the VL, though it cannot be confused with the adjoining nucleus ventralis medialis (VM) because of the darker aspect of its cells on Nissl-stained sections. The particular interest of this area in our connection will be seen in the next section. As to the lateral boundary of the VL, observation of our Nissl-stained material showed a more restricted distribution of the big, heavily-stained cells of the VPL than assumed by Jasper and Ajmone Marsan is. Thus, in good agreement with Rinvik's 2a description, we consider the VL as having a wider caudal and lateral extent than given in the atlas is. Rostrally, the VL is bounded by the nucleus ventralis anterior (VA). Though the cells in the latter nucleus appear sparser and paler stained by cresyl violet, the boundary between the two nuclei seems difficult to ascertain, an opinion shared by Gerhard la, on rabbit. However, the border between VA and VL would seem (as shown in Fig. 8) to be situated a little more caudally than assumed by Rinvik "5 (his Fig. l). Nevertheless, when making these comparisons, one must keep in mind that no stereotaxic landmarks were used for directing our sectioning. Thus, we cannot assume that, in any of our preparations, the plane of section reproduced that of the atlas is. The same certainly applies to the 'oblique frontal' plane used by Rinvik e5 .27. Such slight differences in the plane of sectioning will be reflected in the aspects of the various nuclei and, to some extent, explain the variation in the interpretation. RESULTS

We shall first report the observations made on cases of extensive lesions of the nucleus medialis. Then will be considered what further details are presented by the analysis of cases of small, more selective, destructions of this nucleus. Case DP 63 (survival 7 days.) Extent of the lesion and intracerebellar course o f the fibres. The cerebellum was cut horizontally. The lesion (Fig. 1) has destroyed the caudal pole of the nucleus, including the SMP of Flood and Jansen 14, and almost the whole of the caudodorsal 'horn'. Intracerebellar course. In the neighbourhood of the lesion, a number of degenerating fibres are oriented caudorostrally, extending to rostral parts of the nucleus, p~rticu[arly in its lateral part. In front of the nucleus, the fibres curve in towards the midline, which they cross with the mass of uncinate fibres (Fig. 2). At this level, Brain Research, 24 (1970) 49-68

52

P. ANGAUT AND D. BOWSHER

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Fig. 1. Two cases of medial cerebellar nuclear lesion. Left. case DP 20. cerebellum cut transversely. Above and below respectively, sections passing through the rostral and caudal limits of the lesion. In this and succeeding figures: black cell loss; hatched = regions presenting a glial reaction. Centre figure: photograph of the sections passing through the lesion at its widest extent. Serial slide numbers are given against each figure, so that the extent of the lesions can be appreciated. Right, case DP 63, cerebellum cut horizontally. Same method of representation as on left. The upper and lower figures represent the dorsal and ventral limits of the lesion. For abbreviations used in this and following figures see p. 66.

degenerating fibres are f o u n d particularly in the dorsal part o f the decussation Thence the fibres g a i n the superior cerebellar peduncle contralateral to their side of origin.

Extracerebellar course of the ascending degeneration (Fig. 3). The block comprising b r a i n stem a n d d i e n c e p h a l o n has been cut horizontally, Ascending degenerating fibres leave the cerebellum b y way of the contralateral superior cerebetlar peduncle: Brain Research, 24 (1970) 49-68

ASCENDING FASTIG~AL PROJECTIONS

53

Fig. 2. Case DP 63. Left, photomicrograph of a horizontal section of the cerebellum at the level of the commissural zone. The rostral part of the contour of the medial cerebellar nucleus is indicated by interrupted lines. Nauta method. Right, photomicrograph, at greater magnification, of the region inset on the left, showing degenerating fibres crossing the midline in the cerebellar commissure.

within the peduncle, the degenerating fibres cap the brachium conjunctivum on its dorsomedial aspect. Further rostrally, these fibres do not accompany the brachium conjunctivum as it sinks ventrally in the brain stem, but follow a much more dorsal course throughout the length of the midbrain. Somewhat more medially, efferent fibres from the medial cerebellar nucleus form a diffuse bundle on the ventrolateral border of the central gray matter, roughly in the horizontal plane H-1 of the atlas of Verhaart3L The course of these fibres is parallel to that of the medial longitudinal bundle, which they accompany dorsolaterally. During their course through the midbrain, the fastigiofugal fibres do not give off any branches ventrally in the direction of the red nucleus. In middle and anterior mesencephalic planes, some fibres leave the main bundle to gain the region of the superior colliculus. A not insignificant number of these re-cross the midline in the commissure of the superior colliculus (Fig. 3). All these dorsally-placed degenerating fibres appear to terminate within the colliculus; however, greater detail on this point can be seen in transverse sections, to which further reference will be made in the description of case DP 20 (vide infra). Within the thalamus, ascending fastigiofugal fibres traverse the ventromedial part of the centrum medianum (CM), passing laterally to the habenulo-interpeduncular tract (fasciculus retroflexus) and thus reach the ventromedial zone of the ventrolateral nucleus (VL) and the ventromedial nucleus (VM), where they ramify and mostly terminate. In addition, a small but significant number of fibres, after having crossed the CM, turn towards the midline and cross it. This re-crossed contingent (ipsilateral with respect to the lesion) is distributed to zones of VM and VL, symmetrical to those of the contralateral side. Terminal degeneration. In the mesencephalon, a few terminals are encountered in the medialmost regions of the superior colliculus (Fig. 3, sections 24-27) almost essentially contralateral to the lesion. In the diencephalon, the bulk of the terminal degeneration is found medially within the ventral thalamus, bilaterally (Fig. 3,

Brain Research, 24 (1970) 49 68

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Fig. 4. Projection drawings of largest extent of lesion in four cases of small lesions. DP 18 and 19, above, are cut transversely; DP 41 and 36, below, are cut horizontally. sections 19-22). This area corresponds to the VM and medialmost VL; still abundant degeneration is seen in more dorsal sections, with a more rostral location (Fig. 3, sections 24 and 25). We were not able to determine, in the plane of section here chosen, whether this rostrodorsal extent of the projection area lies in the VL or in VA. A very few telminals are also observed in the nucleus reuniens, among the fibres crossing midline (Fig. 3, section 21). Thus, the thalamic degeneration here observed appears to concern almost symmetrical nuclear regions, but the density of terminals is much higher on the side contralateral to the lesion than the homolateral, i.e. that receiving the re-crossed contingent.

Case DP 20 (survival 10 days) Extent of the lesion (Fig. 1). Both the cerebellum and the brain stem were cut transversely. The caudal half of the nucleus has suffered extensive destruction, and only a thin strip of cells remains untouched, laterally. Ascending degeneration. Indeed, the brain stem trajectory of the fibres cannot be so clearly seen in this case as in a horizontal series. However, black grains, representing transversely-cut fibres, can be seen dorsal to the contralateral brachium conjunctivum in the superior cerebellar peduncle (Fig. 5). (It is the form here assumed by the efferent bundle that caused it to be called the 'hook bundle'29.) Leaving the hook bundle on its lateral aspect, a small number of fibres can be seen passing ventrally Brain Research, 24 (1970) 49-68

56

P. A N G A U T A N D 1). B O W S H E R

Fig. 5. Photomicrograph of superior cerebellar peduncles from case DP 20. On the right, transversely cut degenerating fibres can be seen in the hook bundle, although there is no degeneration on tile left. The dorsal limit or the brachium conjunctivum is indicated, by broken lines.

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Fig. 6. Case DP 20. Projection drawings to show distribution of degeneration in brain stem and diencephalon. Symbols as for Fig. 3. Note bilateral degeneration in superior colticulus and ventrolaterat thalamic nucleus. (Fig. 6) to innervate the vestibular nuclei a n d d o r s a l reticular f o r m a t i o n . These fibies u n d o u b t e d l y represent r o s t r a l m o s t axons o f the uncinate fascicutus, and as such are o f no further concern t o the present work. In the m i d d l e a n d a n t e r i o r p a r t o f t h e m i d b r a i n , an i m p o r t a n t n u m b e r of fibres o f fairly fine d i a m e t e r for the m o s t p a r t describe a v e n t r o d o r s a l curve a r o u n d the griseum centrale. In the form o f a loose fasciculus, these fibres, incorlz.orated in the Brain Research, 24 (1970) 49-68

ASCENDING FASTIGIAL PROJECTIONS

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Fig. 7. Case DP 20. Photomicrograph of the midline thalamic region showing degenerating fibres close to their crossing. Some give off terminals in the nuc[eus reuniens.

stratum medullare profundum of the superior colliculus, reach the midline. Some of them cross the midline, partly in the commissure of the superior colliculus, lzartly in the posterior commissure immediately rostral to it. After decussating, these fibres invade the stratum medullale profundum of the other side (Fig. 6), though collaterals e a v e the bundle on both sides. This dorsal mesencephalic degeneration does not appear to extend beyond the limits of the superioT colliculus. The distribution of these fibles within the colliculus will be described in the next section. At thalamic level, the plane of section used in this series made it possible to follow fibres on the ventral surface of the internal medullary lamina, arborizing laterally into the VM and VL (Fig. 8, left). Other degenerating fibres cross the midline across nn. centralis medialis (NCM) and reuniens (Fig. 7) to be distributed into the VM and VL of the side ipsilateral to the cerebellar lesion. These observations entirely corroborate the results obtained in case DP 63 as described above. Terminal degeneration. Two mesencephalic structures receive projections from the medial cerebellar nucleus the superior colliculus and the griseum centrale. Although contiguous, the former projection is quantitatively much more conspicuous than the latter. In the superior colliculus, degeneration is bilateral. The density is slightly heavier on the right side (contralateral to the lesion), where the extent of preterminal degeneration is also heavier. The diameter of the fibres is medium to fine on both sides. On the right side, a number of fibres of passage (collaterals of the commissural fibres) follow a radial orientation. Preterminal degeneration appears round these fibres, with a mediolateral density gradient. Thus the heaviest degeneration is found, following an arc of a circle around the central gray matter, in the medial Brain Research, 24 (1970) 49 68

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P. ANGAUT AND I). BOWSHER

DP20

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zone of the superior colliculus, corresponding to the stratum griseum profundum of Winkler and Potter a7. There is virtually no degeneration in the more superficial layers of the superior colliculus (Fig. 6). On the left side. the projection is also limited to the stratum griseum profundum, particularly its rostral and dorsal parts. These fastigiotectal projections do not appear to overlap, to any significant extent, on either side, into the nucleus of the posterior commissure. In the griseum centrale, very fine preterminal degeneration, of very feeble density, can be observed on the side contralateral to the lesion. It is found in the lateralmost part of the dorsal quadrant of this structure, i.e. the region neighbouring the commissural fibres. Brain Research, 24 (1970) 49-68

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ASCENDING FASTIGIAL PROJECTIONS

The caudal parts of the thalamus contain no preterminal degeneration. However, a very small number of fine degenerating fibres is found in the rostroventral part of the contralateral CM. Further rostrally, a very small number of degenerating preterminals is present in the nucleus reuniens, near the crossing fibres described in the previous section. in contrast, a zone of dense terminal degeneration occurs in the region of the ventrolateral and ventromedial nuclei. These two nuclei thus represent far and away the most important area of termination of ascending fastigiofugal fibres. The diameter of the degenerating fibres is very variable, but overall is much greater than in the tectal projection area. On the side contralateral to the lesion, the degeneration is quite dense, especially dorsomedially. In the VL, the zone of preterminal degeneration presents itself as a medially-placed band, reaching, rostrally, the dorsalmost parts of the nucleus (Fig. 8, left). The region thus more or less circumscribed corresponds to the medial VL strip distinguished by its paler appearance (see Methods). In this alea the diameter of the fibres seems greater than in the VM (Fig. 11). Furthermore, there is a concentration of preterminal arborizations in the immediate neighbourhood of cell bodies, giving the impression that the projection of the medial cerebellar nucleus on the VL is, at least in great part, axo-somatic (Fig. 11). The lateral half of the VL is free of degeneration. On the same side as the cerebellar lesion, the thalamic degeneration is incomparably less dense. Only a small number of fibres is seen in the dorsal VM and the medial VL. No degeneration was observed in the thalamus apaI t from those regions described above, in particular, it should be noted that no degeneration is seen caudally in the CM, rostrally, in the VA, nor ventral to the thalamus in the fields of Forel or the zona incerta. It cannot be completely excluded that there may exist a very small number of terminations at these levels - - particularly in the VA - - which because of their small diameter or very sparse density have not been revealed in the present material. Further results obtained from the examination o f cases with small lesions

Degeneration in these cases was always found within the terminal regions described in cases with large lesions. Case DP 19 (survival 10 days) shows a small lesion in the medial part of the caudal pole of the nucleus (Fig. 4). Virtually no terminal degeneration is seen in the superior colliculus. In the thalamus (Fig. 8), degeneration is much less abundant than in case DP 20, and is seen in the VM and particularly in the adjacent regions of the VL. Case DP 18 (survival 10 days) exhibits a lesion about double the volume of that in case DP 19, occupying an area somewhat rostral and lateral to that of the preceding case (Fig. 4). Terminal degeneration in the superior colliculus, although less dense than in case DP 20, is nevertheless noteworthy, and appears to have a similar distribution. In the thalamus, degeneration, slightly heavier than in case DP 19, is more dorsally distributed than in this case and is thus much lighter in the VM (Fig. 8). Brain Research, 24 (1970) 49-68

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P. ANGAUT AND I)o BOWS[IER DP 30

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Fig. 10. Projection drawings of horizontal sections from cases DP 36 (above) and DP 41 (below) to show distribution of degeneration within the thalamus. Cases DP 36 (survival 7 days) and DP 4l (survival 7 days) show lesions in the caudalmost part o f the medial nucleus (Fig. 4). Both brains were cut horizontally. The volume o f tissue destroyed is similar in both, but the lesion in case D P 36 is situated more dorsally and more medially than in DP 41. N o significant terminal degeneration is seen in the superior colticulus in either. Neither case shows heavy degeneration in the thalamus, but it is slightly heavier and shows a slightly greater ventromedial extension in D P 4l than in D P 36 (Fig. 10). Brain Research, 24 (1970) 49-68

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A comparison of the results obtained in the different cases just reported reveals important peculiarities of the fibre system under study. First, they are highly suggestive of a differential origin of the fastigiotectal and the fastigiothalamic projections within the nucleus. Thus, cases with small lesions of the caudalmost part of the medial cerebellar nucleus (DP 19, 36, 41 ; Fig. 4) show, in accord with observations made on case DP 63, degeneration which is notable in the thalamus (Figs. 8 and 10) but minimal in the superior colliculi. On the other hand, cases with lesions more rostrally placed (DP 18, 20 in Figs. 1, 4 and 8) show heavier degeneration in the co[liculus. While it would be impossible to delimit specific 'areas' within the caudal half of the medial cerebellar nucleus, it appears highly probable that the cells giving rise to fibres projecting to the V M - V L are more caudally placed than those projecting on to the superior colliculus. Another point that seems worthy of mention concerns the distribution of the fastigiothalamic fibres. Only the contralateral projections will be considered here, as the feeble density of the ipsilateral terminations does not seem to justify its separate treatment: moreover, its distribution appears symmetrical with that on the contralateral side. It has been noted that it is mainly the caudal pole of the medial cerebellar nucleus which projects to the V M - V L : fortunately, it has been possible to make a number of very small lesions in this region (cases DP 19, 36, 41). While there is no marked divergence in the thalamic distribution between these cases, certain differences nevertheless merit discussion. Thus, in cases DP 19 and 36 (Fig. 4), where the lesions are very medial, the heaviest and most extensive degeneration is found in the VL (Figs. 8 and 10); while, conversely, case DP 41, where the lesion is ratheJ lateral (Fig. 4), shows heavier degeneration in the VM (Fig. 10). Similarly, case DP 20 shows

Fig. II. Case DP 20. Photomicrographs of degenerating fibres in right (contralateral) thalamus. Left, ventromedial nucleus; right, ventrolateral nucleus. Brain Research, 24 (1970) 49 68

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P. ANGAUTAND D. BOWSHER

denser and more extensive degeneration in the VM (Fig. 8, left) than case DP 18 (Fig. 8, right), in which the lesion is less extensive caudolaterally. These observations support the idea that medial nuclear projections to the VM and VL respectively do not arise from the same regions. Thus, at least in part, terminals in the two thalamic nuclei do not represent collaterals of single stem fibres, but rather arborizations from neurones in neighbouiing regions of the medial cerebellar nucleus. This may also explain the differences seen n the diameters of terminal arborizations in the VM and VL respectively, the latter being slightly thicker {Fig. t l ). The notion that the fastigio-VM and fastigio-VL projections represent separate systems, both with cells of origin lying in the caudal pole of the medial cerebellar nucleus, while far from proven, may help in the understanding of functional differentiation between the VM and the VL. In favour of such a distinction within the nucleus of origin is the slightly different calibre of VM and VL terminals: it may be noted that Flood and Jansen 14 distinguished, on a cytoarchitectonic basis, a ventrolateral subdivision (their SMP) of the medial cerebellar nucleus, and that lhis part can also be differentiated from neighbouring zones by its afferent connections!. Albeit imprecisely, careful examination of the present material seems to establish a relationship between the extent of damage to the SMP and the density of degeneration in the contralateral VM. As a corollary to this, there also appears to be a relationship between damage to those parts of the medial cerebellar nucleus medial (and dorsal) to the SMP and degeneration in the VI.. In two other cases, only rostral regions of the medial nucleus had been injured. No ensuing degeneration of any importance has been observed along the ascending pathway. Thus, case D P 30 (survival 10 days) shows a very small lesion (Fig, 9) in the region of the commissural fibres rostral to the medial nucleus. This case shows very little degeneration, though degenerating fibres ale found in both the superior cerebellar peduncles, and in a'l the projection zones described previously. These are interpreted as consecutive to interruption, near their crossing, of uncinate fibres originating in either medial nucleus. Case D P 33 (survival 10 days) has a lesion (Fig. 9) involving the rostral onethird of the nucleus, of which a little less than the medial half has been destroyed. No significant degeneration was seen in any of the pathways or terminal zones studied. Even here, part of the small amount of degeneration observed might result flora the interruption by the lesion of fibres originating further caudally in the nucleus. DISCUSSION The present study has shown that the caudal half of the medial cerebellar nUcleus gives rise to the bulk of the ascending fastigial projections. All these fibres decussate within the cerebellum and leave by the superior cerebellar peduncle contrataterai t o their side of origin. In fact, whatever the extent of the lesion within t h e nuCleus, degeneration has only been seen in the ipsilateral superior peduncle when commissurat fibres, rostral to the nucleus, have also been destroyed. Although the ascending fastigial efferents accompany the brachium conjunctivum in the peduncle itself, Brain Research, 24 (1970) 49-68

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they become separated from it in the midbrain. The efferent pathway follows a discrete mesencephalic trajectory, well dorsal to the brachium conjunctivum, and does not undergo decussation at this level. The destination of this efferent pathway appears to us limited to two regions, namely the mesencephalic superior colliculus and the thalamic VM-VL; distribution at both levels is bilateral. No significant projection is seen on to any other structure, such as the midbrain reticular formation or thalamic centre median, even after the most extensive lesions. Further it appears to us that, within the caudal half of the medial nucleus, cells giving rise to the fastigiotectal projections do not seem to be those projecting upon thalamic nuclei, but would be located more rostrally. We shall now discuss the data from the literature and consider what information the present study has brought forward. In the course of the discussion, we shah try to elucidate some questions of nomenclature with which we are faced when comparing data from the classical works. Certainly, there is far from being agreement about either origin, course, or termination of ascending fastigial projections in the many articles devoted to the subject. Despite disagreement as to the uni- or bilateral origin of the ascending efferent bundle and the confusing multiplicity of terms employed to describe the same ascending fibres in their trajectory, it is essentially the question of termination which is most disputed in the literature.

Crossed nuclear origin of ascending fastigial fibres Marchi gave the first description of a direct ascending cerebellofugal pathway in the brain stem, and Russell 29 described its course, in the superior cerebellar peduncle, as a 'hook bundle' capping the brachium conjunctivum without being intermixed with it. Many authors are agreed about the presence of a direct ascending fastigiofugal pathway in the brain stem, though few have given a precise description. The analysis of Probst z2 remains one of the most remarkable in its description of both course and termination. The diversity of nomenclature used by earlier authors remains a source of confusion. Probst calls the pathway he described the 'accessorische BindearmBfindel'. Many later authorsl0,z4, 31 call it the 'uncrossed ascending limb of the brachium conj unctivum'. The expression 'ascending branch of the uncinate fasciculus', as used by Rand ~3, McMasters and RusseP, Carpenter et al2, and Voogd 34, appears to be preferable. There is little real contradiction between these authors, whether they follow the nomenclature of Probst 22 or of Rand z3, the difference being basically semantic. All workers recognize the existence of an ascending fastigial pathway, running through the brain stem dorsal to the brachium conjunctivum without decussating. The complete concordance of the present findings on the course followed in the midbrain with those of Probst 22 is worthy of note.

Destination of ascending fastigial efferents In this field, previous results are discordant. This is doubtless due in part to the Brain Research, 24 (1970) 49-68

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e . A N G A U T A N D D. B O W S H E R

widespread use of the Marchi method, which fails to stain fine fibres, especially near their point of termination. A brief review of earlier findings may be compared with the present results. M i d b r a i n . Although Rasmussen e4 was unable to follow fastigial efferents beyond the mesencephalic reticular formation, Probst 2z had already described projections to the region of the posterior commissure, and noted that some fibres crossed the midline at this point; he believed these fibres to be collaterals of fastigiothatamic axons. Rand 23, Thomas et al. 3l and Cohen et al. ~1 had also noted projection to the region of the posterior commissure, and Rand e3 considered this to be the rostralmost termination of fastigiofugal fibres. Voogd 3'a described 'uncinate' projections bilaterally on the superior colliculus and posterior commissural region, without being able to determine the precise site of termination. With small selective lesions, it has been possible to establish in the present study the bilateral asymmetrical distribution of fastigiotectal fibres to the stratum griseum profundum. It should particularly be noted that the nuclear zone giving rise to the fastigio-collicular fibres, i.e. the most rostral part of the caudal half, receives most of its afferents from Larsell's lobule VII (ref. 35), and that this cortical zone in its turn is predominantly under tectal influence13,30. These data suggest the existence of a tecto-cerebello-tectal loop whose probable influence on certain motor functions ('visuelle Greifreflex' of Hess 16) has recently been examined by one of us ~. T h a l a m u s . Most authors considered the CM, or the intralaminar nuclei, to be the principal site of termination of fastigiotha[amic fibres8,1°, 20,3a. According to the present findings, the CM is traversed by fibres of passage going to the VL, but exhibits a negligible quantity of terminal degeneration. It is probably these fibres of passage that have been observed by previous authors, using the Marchi method. The present study, however, indicates that, apart from the VL and VM, only the NCM and the n. reuniens receive, again in minimal amounts, terminal afferents from the medial cerebellar nucleus. Probst ~" first observed bilateral fastigiofugal terminations in the 'ventral a' nucleus of Von Monakow, which is the VL of our nomenclature (see his Fig. 8): this has been confirmed by more recent authors ~,31,34. Although Voogd 34 described a more extensive terminal region than that found in the present study, he does not appear clearly to have seen a re-crossed thalamic projection. Most authors explain the bilateral distribution by a partial decussation in the posterior commissure. The present results are in contradiction with this opinion, the fibres in the posterlor commissure principally innervating the superior colliculus and to a much lesser extent the nucleus of the posterior commissure: a second, numerically less important, group of commissural fibres exists in the thalamic VL region; the presence of this decussation across the n. reuniens appears not to have been observed by previous authors. However, fibres of cerebellar origin have been observed in the thalamic decussation ('commissure molle" of Vogt a3) without their fasti~ial origin being recognized. Despite the quantitative sparsity of the second (thalamic) decussation, the fact that there are two zones of crossing along the ascending fastigiofugal pathway would appear Brain Research, 24 (1970) 49-68

ASCENDING FASTIGIAL PROJECTIONS

65

to have great functional interest, for it permits the elaboration of two hypotheses concerning the mesencephalic and thalamic distributions. The first, enunciated by Probst 22, maintains that the two terminal projections are collaterals of one another, while the present findings indicate that they are independent and have differential origins within the medial cerebellar nucleus. Functional correlations The question of fastigiotectal projections has been briefly commented upon elsewhere I. It is intended here to consider more particularly the functional significance of fastigial efferents to the thalamic VL, the principal relay to the motor cortex 19. As our results show, the medial cerebellar nucleus projects only to the medialmost region of the VL and the neighbouring VM. Although mainly crossed, fibres reach the thalamus bilaterally from one side of the cerebellum. Furthermore, it has also been shown by one of us ~,a, that the brachium conjunctivum terminates in more lateral parts of the VL. This distribution must certainly confer different properties on the thalamic regions concerned. Anatomically, this organization was expected to be reflected in the efferents of the VL. Macchi 19 found no organization within the VL-motor cortex fibre relation. However, in a physiological analysis of this projection, Rispail-Padel and Massion 2s showed the medial region of the VL to project on to parts of the precruciate cortex (the area 6) that are responsible of the motricity of the axial and proximal musculature, according to Woolsey as. Upon this medial region of the VL, and to some extent the VM, notable cortical projections have been demonstrated to converge (particularly 26, 28). In his extensive anatomical study, Rinvik e6 saw that some of these fibres originate in area 6 (his Figs. 5 and 8). Thus, there would exist a feedback system between the medial VL and the cortical area 6. Rispail-Padel and Massion 2s confirmed this point. Further, they detected the highly topical organization of this loop relation and the excitatory nature of the cortical impulse. On the other hand, Rinvik 27 has demonstrated the presence of other cortical sources of projections to the medial VL, namely the gyrus proreus and, bilaterally, the medial wall of the precruciate gyrus. Thus a number of influences converge upon the cells in the medial VL. While we know that those from the cerebellum ,5, the cortical area 6 (ref. 28) as well as the pallidum ~2, are excitatory, it would be of interest to investigate the role of the others and to see how these various influences are integrated at the thalamic level. SUMMARY

(1) Small stereotaxic lesions were placed unilaterally in the medial cerebellar (fastigial) nucleus of cats; the course and termination of ascending degeneration was subsequently traced by the method of Nauta. (2) Ascending efferents arise almost entirely from the caudal half of the nucleus. All fibres decussate in the cerebellum, and pass out in the contralateral superior peduncle. Brain Research, 24 (1970) 49-68

66

I,. ANGAUT AND D. BOWSHER (3) In the m i d b r a i n , fastigial afferents pass d o r s a l to the b r a c h i u m c o n j u n c t i v u m ;

s o m e t e r m i n a l s are d i s t r i b u t e d to t h e d e e p layers o f the s u p e r i o r c o l l i c u l u s o f b o t h sides. (4) In the t h a l a m u s ,

s y m m e t r i c a l bilateral d e g e n e r a t i o n

is f o u n d in t h e n.

v e n t r a l i s m e d i a l i s a n d the a d j a c e n t m e d i a l p a r t o f the n. v e n t r a l i s l a t e r a l i s ; d e g e n e r a t i o n is m u c h m o r e d e n s e in the side o f t h e t h a l a m u s c o n t r a l a t e r a l to t h e c e r e b e l l a r lesion. (5) T h e r e is n o significant d e g e n e r a t i o n in the m i d b r a i n r e t i c u l a r f o r m a t i o n , c e n t r u m m e d i a n u m , n. v e n t r a l i s a n t e l i o r o r z o n a incerta. (6) D i f f e r e n t i a l origins, t h e o r g a n i z a t i o n , a n d f u n c t i o n a l i m p l i c a t i o n s are discussed.

LIST OF ABBREVIATIONS USED AM AV BC BP CCS CI CL CM CS DBC Flm GC GL GM IA IP L LM LP M MD

= = = = = = = =

nucleusanteromedialis nucleus anteroventralis brachium conjunctivum brachium pontis commissuracolliculisuperioris colliculus inferior nucleus centralis lateralis nucleus centre m6dian colliculus superior decussatio brachiorum conjunctivorum fasciculus longitudinalis medialis ~ griseum centrale corpus geniculatum laterale -- corpus geniculatum mediale : nucleus interpositus anterior (cerebelli) ~nucleus interpositus posterior (cerebelli) - nucleus lateralis (cerebelli) .... lemniscus medialis :: lelnniscus lateralis posterior nucleus medialis (cerebelli) nucleus mediodorsalis

MV NCM N LL NR NSL OS P PC R Re RP RT SGP SMP

nucleus masticatorius =- nucleus centralis medialis ~-- nucleus of the lemniscus lateralis --~:nucleus ruber nucleus subthalamicus luysi nucleus olivaris superior pons nucleus paracentralis nucleus reticularis thalami nucleus reuniens -: nucleus raphe pontis .... nucleus reticularis tegmenti pontis - stratum griseum profundum --subnucleus medialis pars parvocellularis SN -- substantia nigra Thp - tractus habenulointerpeduncularis To tractus opticus VA ~- nucleus ventralis anterior nucleus ventralis lateralis VL VM ~: nucleus ventralis medialis nucleus ventralis posterotateralis VPL VPM = nucleus ventralis posteromediatis -

ACKNOWLEDGEMENTS T h a n k s are d u e to M m e s . L a p l a n t e a n d T h i e s s o n f o r t h e p r e p a r a t i o n o f sections, to M m e s . P o m m e p u y a n d V o u g i e r f o r t h e c a r e o f o p e r a t e d a n i m a l s , to M i s s T r i n s o n f o r the i l l u s t r a t i o n a n d to M r . K a n d a r o u n f o r the p h o t o g r a p h y .

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