Organization of vestibulo-oculomotor projections in the cat

BRAIN RESEARCH

159

ORGANIZATION OF VESTIBULO-OCULOMOTOR PROJECTIONS IN THE CAT

EDWARD TARLOV* Anatomical Institute, Oslo (Norway)

(Accepted November29th, 1969)

INTRODUCTION Detailed investigations have revealed a highly specialized anatomical organization of the connections between the individual vestibular nuclei and the spinal cord 24, the cerebellum2, 9, the contralateral vestibular nuclei and the reticular formation 17, and the labyrinth3°,37. In contrast to the relative precision with which these connections are known, previous studies of the secondary vestibular projections from the individual vestibular nuclei to the motor nuclei of the III, IV and VI cranial nerves are in disagreement on almost all major points. Some authors have indicated that the projections to the extraocular motor (EOM) nuclei arise in all four of the main vestibular nuclei 2°, while others have shown such projections arising only in the medial and superior vestibular nuclei 15, the medial, lateral and superior nuclei 10 or the medial, superior and descending nuclei 26. Regarding the course of ascending fibers from these nuclei there has been divergence of opinion; while it is agreed that the superior vestibular nucleus projects ascending fibers only in the ipsilateral medial longitudinal fasciculus (MLF), the ascending projection from the medial vestibular nucleus has been said to be contralateral by some 15,26 and bilateral by otherslO,14,2°. Axons from the descending vestibular nucleus are said to ascend only in the contralateral MLF by Rasmussen 28, while they have been described as ascending in the ipsilateral MLF by others 2o. Fibers from the lateral vestibular nucleus are said by some authors to ascend bilaterallyXO,3o, but previous studieslS, 26 do not mention their existence. Regarding the terminations of secondary vestibular axons in the EOM nuclei, there has also been a widely divergent opinion, and while some of the differences may be due to the unsuitability of the Marchi method for exact delimitation ofpreterminal axon distribution, there have been marked differences in the results of authors who * Present address: NeurosurgicalService, MassachusettsGeneral Hospital, Boston 02114, Mass., U.S.A. Brain Research, 20 (1970) 159-179

160

F. xn R[,OV

have used the Nauta technique. Szent~gothai 33 and McMasters e t al. "-° have described projections to differing limited areas within the EOM nuclei. Regarding the projections to the interstitial nuclei of Cajal and the nuclei of Darkschewitsch, these terms have not been used in the same sense by all authors and, therefore, findings cannot readily be compared. I have recently reviewed this subject in a study of the rostral limits of the secondary vestibular projections 3~. Apart from the discrepancies due to limitations of the Marchi method and those due to the lack of a standardized nomenclature for the vestibular nuclei in earlier studies, the differences among these experimental observations are largely due to varied interpretations of degenerated fibers which result from unrecognized injuries outside the intended target, due either to the electrode track, to the trauma inflicted upon the vestibular nuclei and other structures during open operation within the fourth ventricle or to slight but significant extension of the lesions into adjacent vestibular nuclei. Incidental damage outside the intended target may be evaluated by using a variety of approaches in making the lesions, and by examining sections cut in a plane parallel to the course of degenerated fibers being studied. Neither of these techniques has apparently been used in establishing the many differing views summarized above. The present research was designed to study the pattern of rostral projection of each of the four main vestibular nuclei, with particular attention to controlling the extent of the lesions and damage to surrounding structures. The Nauta 2z technique of staining degenerated axons was employed because of its relative advantages in determining the distribution of fiber projections. MATERIAL AND METHODS

Unilateral stereotaxic lesions were placed in restricted portions of the vestibular nuclei of 17 cats. The stereotaxic coordinates were based on those devised through the efforts of a number of workers at the Anatomical Institute, particularly Drs. O. Pompeiano, R. Nyberg-Hansen and R. Ladpli. The coordinates given in the cat stereotaxic atlases o f Snider and Niemer 29 and Berman 4 are not accurate for the individual vestibular nuclei. In order to evaluate subsequently degenerated fibers from damage outside the vestibular nuclei, the electrode was introduced at a variety of angles. In some cases it was passed horizontally into the vestibular nuclei via a small burr hole above the posterior rim of the foramen magnum through the cortex o f the inferior vermis and through the fourth ventricle, an approach which minimizes damage outside the vestibular nuclei and avoids the deep cerebellar nuclei and their efferent tracts. In the majority of the cases, the electrode was angled 60 ° posteriorly in the sagittal plane to avoid the tentorium. In some cases a lateral angulation of up to 15° in the coronal plane was used as well. A comparison of the results with such a variety of electrode approaches, some of which produced no damage to any structure outside the target and the superficial cerebellar cortex, made it possible to assess fully the consequences of the lesion produced by the electrode track. It is essential to avoid Brain Research,

20 (1970) 159-179

ORGANIZATION OF VESTIBULO-OCULOMOTOR PROJECTIONS

161

surgical exposure of the posterior column nuclei and the vestibular nuclei themselves because of the extreme sensitivity of the Nauta method of staining degenerated axons. Even the most careful elevation of the vermis and exposure of the fourth ventricle may produce definite ascending Nauta degeneration from the posterior column and vestibular nuclei. The temperaments of the cats used did not permit satisfactory postoperative neurological examination. Most of the cats were allowed to survive for between 5 and 7 days after operation. In a few cases, shorter survival times of 3 and 4 days were used. Closely spaced serial, horizontal, 25 #m thick frozen sections were stained with the Nauta ~3 method to demonstrate degenerated axons. From the nuclei of the posterior commissure to the ventral border of the abducens nucleus, the sections were taken at 125 #m intervals, while those through the remainder of the brainstem and the thalamus were 250 b~m apart. Thionin staining was carried out on sections through regions where nuclear boundaries could not easily be recognized on the silver sections. The criteria used to identify axon degeneration with the Nauta technique are the same as those stated by Walberg et al.6,as,aT; examples are illustrated in Fig. 10. The nomenclature used for the vestibular complex is that cited in Brodal et al.S; for the oculomotor nuclei, that of Warwicka8; for the interstitial nuclei of Cajal, the nuclei of Darkschewitsch and the nuclei of the posterior commissure, that of Brodal and Pompeiano 7. N o t e s on the oculomotor nuclei

It would be of interest in relation to the distribution of secondary vestibular projections to know the exact locations within the third nerve nuclei of the motor neurons innervating individual muscles, but this information is not available for the cat. The anatomical and physiological literature pertaining to muscle representation within the oculomotor nuclei is critically reviewed in the study of Warwick as. By observing in the monkey the distribution of nerve cells showing acute retrograde changes after extirpation of individual muscles, Warwick demonstrated extraocular muscle motor pools lying in elongated columns extending in a rostrocaudal direction and arranged on a dorsoventral basis, with an entirely crossed representation of the superior rectus in the dorsal, caudal portion of the column and ipsilateral representation from dorsal to ventral of the inferior rectus, the inferior oblique and the medial rectus. The levatores palpebrae were bilaterally represented in the central caudal nucleus. This scheme differs from all those which had been proposed earlier. On many points, the available anatomical data for the cat, much of it obtained in the last century, are more widely divergent from the scheme demonstrated in the monkey than one would expect from species differences alone. For example, the investigations of Abd-EI-Malek I indicated a bilateral representation of all muscles. This and other earlier anatomical studies have been questioned by Warwick 3s on grounds of technique. Studies in which electrical stimuli have been applied to the oculomotor nucleiS,81 Brain Research, 20 (1970) 159-179

162

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do not seem entirely reliable because of the difficulties inherent both in localizing the stimulus and in interpreting individual muscle action from movements of the globe. These drawbacks were largely overcome by Bienfang~, who antidromically stimulated cat oculomotor neurons and found an almost entirely crossed representation of the superior rectus and an ipsilateral representation of the inferior oblique. These physiological findings suggest that a similar representation of certain muscles may exist in the monkey and cat. in order to present the data, the somatic oculomotor nuclei were divided into five regions, represented diagrammatically in Fig. 9C. The boundaries of these regions are similar to the boundaries established by Warwick ss for the groups of III nucleus motor neurons innervating extraocular muscles in the monkey. Precise knowledge of the lower motor neuron innervation of the cat's extraocular muscles must await further anatomical investigation. RESULTS

The superior vestibular nucleus Lesions involving differing portions of the superior vestibular nucleus (SV)

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Fig. 1. Origins of vestibulo-oculomotor projections. Diagrams of serial horizontal sections through the right vestibular nuclei as seen from dorsal surface, representing extent of lesions in each case (numbers). Cross-hatched lesions give rise to degenerated fibers in EOM nuclei. Note that these lie in superior vestibular nucleus and rostral portions of medial vestibular nucleus. Lesions in caudal parts of the medial vestibular nucleus and lesions in the lateral and descending vestibular nuclei (not cross-hatched) did not give rise to degenerated axons in the EOM nuclei.

Brain Research, 20 (1970) 159-179

ORGANIZATIONOF VESTIBULO-OCULOMOTORPROJECTIONS

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following a lesion of central portion of superior vestibular nucleus. Dots indicate preterminal degeneration and wavy lines, fibers of passage. Note ascending fibers from superior vestibular nucleus passing into ipsilateral MLF. Separate degenerated fibers resulting from electrode track through brachium conjunctivum pass to contralateral red nucleus and thalamus. were produced in 5 cases, cats Rove 10, 6, 3, 8 and 23; survival times 5, 7, 7, 6 and 5 days. The extent o f each of the lesions is indicated in Fig. 1. The lesion in case Rove I0 destroys the entire central portion of the SV, extending to its ventral border. The electrode track enters the nucleus from its dorsal surface, having traversed the caudomedial edge o f the superior cerebellar peduncle. There is no evidence o f damage to other vestibular nuclei. From the lesion, degenerated fibers pass medially into the ipsilateral VI nucleus (Fig. 2, 33). It will be noticed from Fig. 3,33 and Fig. 4,26 that no degenerated axons in the ipsilateral VI nucleus were observed in cases Rove 6 and Rove 3, in which lesions of the SV involved only its rostral and dorsal portions respectively. On the other hand, degenerated axons in the ipsilateral VI nucleus were seen in cat Rove 8 (Fig. 5,26-28) where the lesion involves central and caudal parts of the SV and in case Rove 23 (not illustrated), an identical lesion of the SV. A comparison of the distribution of degenerated axons in these cases with differing SV lesions forms the basis for Fig. 9A, in which are represented the regions within the SV projecting to the VI, IV and regions within the III nuclei. For example, the secondary vestibular projection to the ipsilateral abducens Brain Research, 20 (1970) 159-179

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Rove 6 Fig. 3. Rove 6. Lesion in rostral portion of superior vestibular nucleus. Distribution of degenerated axons in E O M nuclei differs from case Rove 10.

nucleus originates in centrocaudal regions of the SV (Fig. 9A, 1) while no projection to the contralateral VI nucleus was observed in any cases with SV lesions (Fig. 9A, 2). From the SV, dense bundles of ascending fibers pass rostromedially into the ipsilateral MLF (Figs. 2-5), from which they distribute to the extraocular motor (EOM) nuclei bilaterally. Those which reach the contralateral IV nucleus deeussate within caudal portions of the III nuclei. The course of ascending fibers from the SV is represented in diagrammatic form in Fig. 6. N o degenerated fibers from the SV were observed in the contralateral MLF. In cat Rove 10, in which the SV lesion is relatively extensive, the degenerated axons are widely distributed throughout all portions of the EOM nuclei bilaterally with the exception noted above of the contralateral VI nucleus (Fig. 2 and Table I). From smaller lesions of the SV (Figs. 3-5), the distribution of degenerated axons in the EOM nuclei is restricted. The projections from areas within the SV to regions within the EOM nuclei differ from case to case according to the location of the lesion in the SV. Some regions within the EOM nuclei apparently receive more extensive projections from portions of the SV than others. The findings summarized in Table I indicate a topical organization of the projections from regions within the Brain Research, 20 (1970) 159-179

ORGANIZATION OF VESTIBULO-OCULOMOTOR PROJECTIONS

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Fig. 4. Rove 3. Lesion in dorsal portion of superior vestibular nucleus. ]Note different distribution of degenerated axons in EOM nuclei compared to preceding 2 cases.

SV to regions within the EOM nuclei. This organization is represented in Fig. 9. Rostral to the oculomotor columns, degenerated fibers are seen bilaterally in the interstitial nuclei of Cajal and the nuclei of Darkschewitsch (Figs. 2-6). These fibers are more numerous on the side of the lesion and are somewhat smaller in caliber than those seen in the EOM nuclei. No degenerated fibers from the SV were observed to pass rostral to the interstitial nuclei of Cajal and the nuclei of Darkschewitsch in case Rove 23, in which a lesion in the superior vestibular nucleus was made by passing the electrode through the fourth ventricle without damaging deep portions of the cerebellum. Degenerated fibers seen in the thalamus in cases Rove 3, 6, 8 and 10 were traced to concomitant damage by the electrode to the deep cerebellar nuclei and their efferent pathways. Degenerated fibers were observed to ascend from the electrode tracks via the brachium conjunctivum across its decussation to the contralateral red nucleus and thence to the ventro-oral thalamus (Figs. 2-5). More extensive damage to the brachium conjunctivum is correlated with more extensive axon degeneration in the contralateral red nucleus and the contralateral thalamic terminus of the brachium conjunctivum. No evidence for the existence o f a vestibulo-thaJamic lemniscus was found. Brain Research, 20 (1970) 159-179

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E. TARLOV

TABLE I SUMMARY OF DISTRIBUTION OF AXON DEGENERATION IN E O M

NUCLEI OF EACH CASE

Approximate relative numbers of degenerated axons indicated by + for slight numbers, + + for moderate and + + + for large numbers of degenerated axons. III nuclei have been subdivided into 5 regions numbered as indicated in Fig. 9. Side*

VI

IV

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Lesions in superior vestibular nucleus

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* I = ipsilateral; C = contralateral. The medial vestibular nucleus

The extent o f f o u r lesions in cats R o v e 9, 4, 5 a n d 22 i n v o l v i n g r o s t r a l p o r t i o n s o f the m e d i a l vestibular nucleus ( R M V ) is i n d i c a t e d in Fig. 1. A r e c o n s t r u c t i o n o f the course a n d d i s t r i b u t i o n o f the d e g e n e r a t e d a x o n s in cases R o v e 9 (survival 5 days) a n d R o v e 5 (survival 7 days) is given in Figs. 7 a n d 8. T h e lesion in case R o v e 4 (survival 7 days), n e a r l y identical to the lesion in case R o v e 5, p r o d u c e d a n e a r l y identical p a t t e r n o f d e g e n e r a t e d a x o n s in the E O M nuclei. F r o m the R M V , d e g e n e r a t e d fibers p a s s m e d i a l l y into the ipsilateral a b d u c e n s nucleus (Figs. 7,39 a n d 8,21-23). A few d e g e n e r a t e d fibers p a s s to the c o n t r a l a t e r a l a b d u c e n s nucleus. A s c e n d i n g d e g e n e r a t e d fibers e n t e r the c o n t r a l a t e r a l M L F . Their t o p i c a l o r g a n i z a t i o n is evident at the d e c u s s a t i o n ; those f r o m m o r e rostral p o r t i o n s o f the R M V m a i n l y cross r o s t r a l to the VI nuclei, while t h o s e f r o m m o r e c a u d a l p a r t s o f t h e r o s t r a l m e d i a l v e s t i b u l a r nucleus cross at a n d b e l o w the level o f the a b ducens nuclei ( c o m p a r e Figs. 7,39 a n d 8,21 ; Fig. 6). N o d e g e n e r a t e d fibers f r o m the R M V a s c e n d in the i p s i l a t e r a l M L F . T h e course o f a s c e n d i n g fibers f r o m the R M V is Brain Research, 20 (1970) 159-179

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ORGANIZATION OF VESTIBULO-OCULOMOTOR PROJECTIONS

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Fig. 5. Rove 8. Lesion in caudal part of superior vestibular nucleus, also damaging lateral vestibular nucleus. Because no degenerated fibers in EOM nuclei were seen with lesions confined to the lateral vestibular nucleus, including portions of the lateral vestibular nucleus injured here, this case demonstrates the projection from the caudal portion of the superior vestibular nucleus.

represented in Fig. 6. Like the superior vestibular nucleus, the RMV projects to the EOM nuclei bilaterally. Ascending fibers from both rostral and caudal parts of the R M V pass into the contralateral IV nucleus. The projection to the contralateral IV nucleus from rostral portions o f the RMV seems less extensive than that from its caudal portions (compare Figs. 7,22 and 8,14). Within the III nuclei, the pattern of degenerated axons differs from rostral to caudal parts of the RMV. For example, the region in the RMV which projects to the ipsilateral region 4 within the III nucleus (Fig. 9) seems to lie further rostrally in the RMV than the area which projects to this region on the contralateral side. These differences (compare Figs. 7 and 8) are represented in diagrammatic form in Fig. 9. Rostral to the oculomotor nuclei, a few degenerated fibers pass into the contralateral interstitial nucleus o f Cajal and the nucleus of Darkschewitsch. This projection appears to be slightly more extensive from the more caudal parts of the RMV (compare Figs. 8,19 and 7,26). The projection to these nuclei from the RMV is mainly crossed. Only a very few fibers are seen on the ipsilateral side; these may cross within upper parts o f the III nuclei, but it is difficult to be entirely certain on this point because o f the very small number o f degenerated fibers involved. In cases Rove 9 Brain Research, 20 (1970) 159-179

168

E. T A R L O V

ND. int.

SUPERIOR VESTIBULAR NUCLEUS

MEDIAL VESTIBULAR NUCLEUS

Fig. 6. Diagrams of courses of vestibulo-oculomotorfibers. Ascendingfibers from superior vestibular nucleus (left) pass in ipsilateral MLF to EOM nuclei bilaterally. Note that fibers to contralateral III and IV nuclei cross midline within III nuclei. In contrast, fibers from medial vestibular nucleus (right) decussate between levels of IV and VI nuclei and ascend entirely in contralateral MLF. Note that distribution of fibers both from superior and medial vestibular nuclei is extensive and bilateral. In MLF, fibers ascending from contralateral medial vestibular nucleus lie medial to fibers ascending from ipsilateral superior vestibular nucleus. Dotted lines indicate sparse projections.

and Rove 22 (survival 5 days), the electrode entered the medial vestibular nucleus without traversing deep portions of the cerebellum. No axon degeneration was observed rostral to the interstitial nuclei of Cajal and the nuclei of Darkschewitsch, while in cases Rove 4 and 5 degenerated fibers in the contralateral red nucleus and thalamus could be traced to damage the brachium conjunctivum. As seen from Fig. 1, lesions in Rove 13, 14, 16 and 18 (survival times 6, 7, 4 and 4 days) involving more caudal parts of the medial vestibular nucleus did not result in degenerated fibers in the EOM nuclei.

The lateral vestibular nucleus This nucleus does not appear to give rise to projections to any o f the EOM nuclei. Lesions confined to the lateral vestibular nucleus were produced in two cases, Rove 7 and Rove 17. The lesion in Rove 7 (survival 6 days) destroys approximately four-fifths of the volume of the lateral vestibular nucleus extending all the way to its ventral boundary. No degenerated axons in the EOM nuclei were observed in

Brain Research, 20 (1970) 159-179

ORGANIZATIONOF VESTIBULO-OCULOMOTORPROJECTIONS

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Fig. 7. Rove 9. Lesion in rostral portion of medial vestibular nucleus. Ascending fibers cross midline rostral to VI nucleus and ascend in contralateral MLF. Lesion in this case made without damage to deep cerebellar nuclei or their efferent tracts. No degenerated fibers above level of nucleus of Darkschewitsch. Decussating fibers pass rostral to VI nuclei into contralateral MLF.

this case. An occasional degenerated axon was seen in the ipsilateral M L F as far rostral as the interstitial nucleus of Cajal. From the needle track through the medial border of the left dentate nucleus, degenerated axons were traced into the brachium conjunctivum, through its decussation to the magnocellular portion o f the contralateral red nucleus and thence to the thalamus. The findings resulting from a nearly identical lesion in Rove 17 (survival 3½ days) did not differ from those in Rove 7.

The descending vestibular nucleus Like the lateral vestibular nucleus, the descending vestibular nucleus does not give rise to projections to the E O M nuclei. Lesions involving the descending nucleus in cases Rove 11, 12, 14 and 16 (survival times 5, 5, 7 and 4 days) are shown in Fig. 1. No degenerated axons in the E O M nuclei were observed in any o f these cases. An occasional degenerated axon was observed in the ipsilateral M L F , passing as far rostrally as the interstitial nucleus of Cajal and the nucleus o f Darkschewitsch. This projection is rather sparse. Few, if any, degenerated fibers were seen in the contralateral interstitial nucleus o f Cajal and the nucleus o f Darkschewitsch.

Brain Research, 20 (1970) 159-179

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E. TARLOV

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Fig. 8. Rove 5. Lesion in medial vestibular nucleus caudal to lesion in Rove 9. Decussation is at and below level of VI nuclei (compare to Rove 9, Fig. 7). Distribution of axon degeneration in EOM nuclei differs from Rove 9.

DISCUSSION

Origins of vestibulo-EO M nuclei projections Because of the risk of injury to fibers passing through the lesions, anterograde degeneration experiments do not necessarily demonstrate the origins of degenerated fibers. However, it seems unlikely that lesions in the SV and R M V injured fibers ascending to the E O M nuclei from the lateral or the descending nuclei because even extensive lesions of the latter nuclei produced no fiber degeneration in the EOM nuclei (Fig. 1). The rather wide separation in the course of ascending fibers from the SV and the R M V (Fig. 6) makes it appear unlikely that discrete lesions of one of these regions will interrupt fibers from the other. Similarly, because of their separate medialward course, small lesions of the upper R M V are rather unlikely to interrupt fibers from the caudal RMV. For these reasons, conclusions about the separateness of the projections from the SV and R M V and from regions within the R M V seem soundly based. With respect to a topical arrangement of projections from areas

Brain Research,20 (1970) 159-179

ORGANIZATION OF VESTIBULO-OCULOMOTOR PROJECTIONS

A.

Superior

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I. Ipsilateral

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171

C. Oculomotor (m') Nuclei

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Fig. 9. Origins and distribution of projections to EOM nuclei. Orientation as in Fig. 1. Within superior vestibular nucleus (A) and medial vestibular nucleus (B) regions which project to ipsilateral (1) and contralateral (2) abducens and trochlear nuclei, and regions within III nuclei (C) are indicated by symbols (Key, lower right). Density of symbols indicates approximate density of axonal degeneration resulting from lesions of these areas. Note the wide and, in most cases, bilateral distribution of projections to EOM nuclei.

within the SV, there is less certainty. Because of the rostral course of its ascending fibers, rostrally situated lesions are rather likely to interrupt fibers from more caudal portions of the SV. Although it seems clear that different patterns ofaxon degeneration in the EOM nuclei result from lesions in different portions of the SV, the exact topography of the origins of these projections is difficult to establish. Efferent fibers from the cerebellum which traverse the vestibular nuclei complicate the study of commissural and reticular formation projections from lesions of the vestibular nuclei (see ref. 17). Although cerebello-oculomotor projections wer~

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172

E. TARLO\:

Fig. 10. A, Horizontal section through maximal extent of lesion in superior vestibular nucleus (Rove 10). Oriented as in Fig. 1 with giant cells of lateral vestibular nucleus caudal to lesion. -< 29. B, Horizontal section through maximal extent of lesion in rostral part of medial vestibular nucleus (Rove 5). Giant cells of lateral vestibular nucleus visible at top of page; heavy bundles of fibers at lower right identify the descending vestibular nucleus. × 29. C and D, Neurons of trochlear nucleus (C) and Ill nucleus (D) with adjacent axon degeneration (Nauta section), x 560.

ORGANIZATIONOF VESTIBULO-OCULOMOTORPROJECTIONS

173

postulated by early workers and have recently been studied by Carpenter and Strominger 11, the existence and distribution of such connections is somewhat in doubt (see Jansen la, Dow and Manni13). It would, of course, not be a simple matter to make lesions of the brachium conjunctivum and ventral portions of the dentate nuclei without injuring the vestibular nuclei, and it is particularly these sites which Carpenter and Strominger 11 have felt, give rise to cerebello-oculomotor connections. For the moment, full knowledge of the nature of the cerebellar input to the oculomotor nuclei must await more detailed investigations of the cerebellum. Since anterograde and retrograde degeneration studies each have their limitations, points upon which there is agreement are strengthened. In agreement with the data presented here, Brodal and Pompeiano 7 found that even lesions of the brainstem which were nearly unilateral produced bilateral changes in the superior and medial vestibular nuclei. The retrograde changes which Brodal and Pompeiano 7 found in the lateral and descending nuclei may have resulted from transection of the few axons observed in this study passing from these nuclei to the nuclei of Darkschewitsch and Cajal; an explanation of the apparent quantitative discrepancy between the very few ascending fibers seen here following lesions of the lateral and descending vestibular nuclei and the relatively more numerous cells with retrograde changes which Brodal and Pompeiano identified in these regions, is not now possible. The restricted origins demonstrated here for vestibulo-EOM nuclei projections correlate rather well with physiological data and with certain anatomical data regarding other vestibular connections. Within the vestibular nuclei, the separate distribution of semicircular canal projections and otolithic organ projections 19 have recently been studied by Stein and Carpenter 8° in the monkey and by Gacek 41 in the cat. These authors have demonstrated that the semicircular canal ganglia project principally to the superior vestibular nucleus and to rostral portions of the medial vestibular nucleus. It is these regions, the present study demonstrates, which project to the EOM nuclei. Gacek found that within the SV the cells lying most medially receive projections from all three semicircular canals, while within central portions of the SV, the anterior and horizontal canals are represented rostrally and laterally while the posterior canal projects caudally and medially. In the medial vestibular nucleus, according to Gacek, the projections of the semicircular canals are not separated. The present study demonstrates differing projections from each of these regions to areas within the EOM nuclei. Both Stein and Carpenter 30 and Gacek 41 found sparse projections from the semicircular canal ganglia to rostral portions of the descending vestibular nucleus, and very occasional degenerated fibers, interpreted as preterminals, in the lateral vestibular nucleus. These regions, the present study demonstrates, send sparse projections to the interstitial nuclei of Cajal and the nuclei of Darkschewitsch but do not send axons to the extraocular muscle motor nuclei. The functional significance of the dual representation of each semicircular canal within both the superior and medial vestibular nuclei is not yet fully understood. Within the medial vestibular nucleus, chiefly in its rostral portions, Wilson e t al. 39,40 Brain Research,

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~z. rARLOV

have found cells which are inhibited from the ipsilateral labyrinth and others which are, in support of the earlier findings of Shimazu and Precht as, inhibited from the contratateral labyrinth. Detailed physiological studies of the superior vestibular nucleus have not been reported. Within the medial vestibular nucleus, the predominantly rostral site of origin of ascending projections indicated by the present data corresponds to the location in the medial nucleus of cells which Wilson et al. 4o could excite antidromically by rostral M L F stimulation. Course o f v e s t i b u l o - E O M nuclei projections

Ascending fibers from the SV and RMV take different courses (Fig. 6). From the RMV, fibers pass medially across the midline into medial portions of the contralateral MLF. Fibers arising in more caudal portions of the RMV decussate at the level of the VI nuclei (Fig. 8), while those from more rostral parts of the RMV pass across the midline just rostral to the VI nuclei (Fig. 7). With respect to their origins, there is thus a topical arrangement within the decussation of the fibers from the RMV. From the SV, fibers pass rostromedially as a dense bundle into the ipsilateral MLF where they ascend in its lateral portions. A topical arrangement is not so apparent in these fibers as in those of the RMV, perhaps in part because the bundles of ascending fibers from the SV are much closer together than those passing medially from the RMV. Within caudal portions of the ascending MLF, between the levels of the IV and III nuclei, the fibers from the ipsilateral SV lie in lateral portions of the MLF, while those from the contralateral RMV lie in its medial portions. At higher levels of the MLF, as fibers stream medially into the Iil nuclei, this arrangement is not clearly apparent. No ascending fibers from the SV were seen in the contralateral MLF, nor were any from the RMV seen ascending in the ipsilateral MLF. In agreement with these findings, crossed projections from the medial vestibular nucleus and ipsilateral ascending pathways from the SV as well as the location of the fibers in the M L F were described by Gray 15. The findings of Ferrarro et al. 14 and McMasters et al. 2° of bilateral ascending M L F degeneration following medial vestibular nucleus lesions may well result from their exposure of the fourth ventricle, a procedure rather likely to traumatize the medial vestibular nuclei bilaterally. The findings of most previous authors who have studied the course of rostral projections of the superior vestibular nucleus 1°,15,2°,26 are in accord with the findings of this study that fibers ascend from the SV only in the ipsilateral MLF. That the number of degenerated fibers in the MLF decreases at successive rostral levels is in accord with the diminishing retrograde changes in the vestibular nuclei following progressively higher lesions of the MLF described by Brodal and Pompeiano 7. Distribution o f degenerated axons in E O M nuclei

Both the SV and RMV have extensive bilateral projections to the EOM nuclei. Brain Research, 20 (1970) 159-179

ORGANIZATION OF VESTIBULO-OCULOMOTOR PROJECTIONS

175

The distribution within the EOM nuclei of projections from small regions within the SV and RMV is represented in diagrammatic form in Fig. 9. The SV and RMV have widely overlapping as well as apparently separate projection fields. These projection fields for the SV and RMV may be even wider within the EOM nuclei than indicated in Table I and Fig. 9. The lack of degenerated preterminals at least in some regions may only be due to the incompleteness of the lesions in the appropriate portions of the SV and RMV; as seen in Fig. 1, not all portions of the SV and RMV are involved by lesions. Within the EOM nuclei are areas where particularly numerous degenerated axons are found following certain lesions. From a comparison of cases, it is evident, for example, that the IV nuclei receive an extensive projection from the ipsilateral SV and, to a lesser extent, from the contralateral RMV, while degenerated axons are most numerous in the VI nuclei following lesions of the rostral part of the ipsilateral RMV. Similarly, within the III nuclei, certain regions receive preferential projections from certain areas within the SV and RMV. The pattern includes considerable bilateral overlapping in the projections from these nuclei (Fig. 9). Fibers crossing the midline at rostral levels do so within the 1II nuclei, as indicated in Fig. 6. It will be noticed in Fig. 6 that fibers from the SV which pass to the contralateral trochlear nucleus decussate through caudal levels of the III nuclei. The topical organization of the projections described here has not been apparent in several studies with the Nauta technique, due perhaps in part to technical factors. For example, McMasters et al. 2o exposed the fourth ventricle in making lesions in the vestibular nuclei. As noted above, slight, even minimal trauma to the exposed medial vestibular nuclei may give rise to axon degeneration subsequently interpreted as resulting from lesions of the lateral and descending nuclei. Furthermore, the length of postoperative survival times is crucial in silver staining of degenerated axons, and when all sections are cut perpendicular to the long axis of the brainstem, ascending degenerated axons passing at right angles to the section may be difficult to recognize. Such factors may explain the discrepant findings of these authors. The projections of the superior vestibular nucleus as described by Szent~tgothai32,33 are, as in McMasters et al. 2o, much less extensive than those described here, where such restricted patterns of degeneration were found only following partial lesions of the SV. Conversely, involvement of other vestibular nuclei outside the intended target may well account for Szent/tgothai's findings of a projection from the lateral vestibular nucleus to the EOM nuclei. The precise extent of the lesions cannot be judged from the illustrations in Szenthgothai's paper. A full review of the actions of the individual extraocular muscles is outside the scope of this paper. It is clear, however, that virtually any movement of the globe must require changes in length of all the extraocular muscles. For example, abduction of the eye must at least involve the contraction of the lateral rectus and the two obliques with inhibition of their antagonists. Furthermore, muscle action changes with the position of the globe; as the globe moves from full adduction to full abduction, the superior oblique is successively a depressor, an abductor and a rotator of the globe. Past attempts at rigid correlation of anatomical vestibulo-EOM nuclei pathways with eye movements in certain directions thus do not seem warranted, and, as noted Brain Research, 20 (1970) 159-179

176

E. TARLO\

above, past findings of limited projections from the SV and RMV to the EOM nuclei may well be the result of incomplete lesions of these vestibular nuclei. In fact, in their recordings of extraocular muscle activity during stimulation of any single semicircular canal nerve, Cohen et al. 12 found evidence that every eye muscle was activated or inhibited. Such widespread vestibular influences on the extraocular motor nuclei could be conducted over the direct vestibulo-EOM nuclei projections described here. The requirements for delicately balanced excitatory and inhibitory interconnections between the vestibular nuclei and EOM nuclei may also be met in part through commissural connections between the vestibular nuclei 17,2s via multisynaptic connections through the reticular formation 18 and through connections with the interstitial nuclei of Cajal and the nuclei of Darkschewitsch (see below). Rostral projections f r o m the vestibular nuclei to other regions

From the SV and RMV, projections to the interstitial nuclei of Cajal and the nuclei of Darkschewitsch were observed. The projection from the SV is mainly ipsilateral, while that from the RMV is mainly crossed (Fig. 6). A very sparse ipsilateral projection to these nuclei from the lateral and descending vestibular nuclei seems to exist. Within the limitations of judging normal fiber size from the size of swollen degenerated axons, the degenerated fibers seen in the nuclei of Darkschewitsch and Cajal seem to be of somewhat smaller caliber than those in the EOM nuclei. It appears from physiological data that connections between the vestibular nuclei and the nuclei of Cajal and Darkschewitsch may be functionally important in certain inhibitory pathways. Following stimulation of the interstitial nucleus of Cajal, an inhibition of the activity of cells in the ipsilateral, superior and medial vestibular nuclei has been recorded21, 22, while stimulation of the nucleus of Darkschewitsch produced an inhibition of activity in all the extraocular muscles 27. Pompeiano and Walberg 25 had found in their Glees study evidence for descending projections from the interstitial nucleus of Cajal to the ipsilateral medial vestibular nucleus, which as the present study indicates sends ascending axons predominantly to the contralateral interstitial nucleus. Techniques such as those described in Walberg's paper a6 may be of use in anatomical identification of excitatory and inhibitory pathways. No degenerated secondary vestibular fibers were observed in any case in the nuclei of the posterior commissure or in any region rostral to this level. Degenerated fibers seen in the red nuclei and the thalamus were traced to concomitant damage to the deep cerebellar nuclei and their efferent pathways and were not seen when such damage was avoided. These findings are similar to my findings in primates, in which a direct vestibulo-thalamic lemniscus does not appear to exist 34. It appears that vestibular sensation which reaches 'higher' levels must pass across synapses perhaps either in the nuclei in the reticular formation which receive vestibular input (see ref. 17) or through the interstitial nuclei of Cajal and the nuclei of Darkschewitsch. The extensive anatomical and physiological literature on this subject is reviewed elsewhere 34. Brain Research, 20(1970) 159-179

177

ORGANIZATION OF VESTIBULO-OCULOMOTOR PROJECTIONS

Fiber size in ascending projections from vestibular nuclei The a p p a r e n t l y s o m e w h a t smaller size o f fibers seen in the interstitial nuclei o f C a j a l a n d the nuclei o f D a r k s c h e w i t s c h has been m e n t i o n e d above. A m o n g the d e g e n e r a t e d axons in the E O M nuclei, no convincing evidence o f differing fiber size p o p u l a t i o n s a m o n g the d e g e n e r a t e d axons in the E O M nuclei could be ascertained. M e n t i o n is m a d e o f this p o i n t b e c a u s e several types o f fibers p a s s i n g to the E O M nuclei have been d e s c r i b e d in G o l g i p r e p a r a t i o n s b y Szenfftgothai 33. H e has interp r e t e d the larger caliber fibers to be s e c o n d a r y v e s t i b u l a r fibers having relatively small p r o j e c t i o n fields a n d involved in direct v e s t i b u l o - o c u l o m o t o r c o n d u c t i o n . The smaller fibers, his studies indicate, arise in the region o f the interstitial nuclei a n d in the reticular f o r m a t i o n a n d d i s t r i b u t e their t e r m i n a l b r a n c h e s over a wide a r e a within the E O M nuclei. The m a t e r i a l here, however, does not include lesions o f these regions o u t s i d e the v e s t i b u l a r nuclei suggested to be the source o f small axons to the E O M nuclei. ABBREVIATIONS EMPLOYED IN TEXT AND FIGURES B.c. D

= brachium conjunctivum = descending (inferior) vestibular nucleus EOM nuclei = extraocular motor nuclei IN = interstitial nucleus of vestibular nerve L = lateral vestibular nucleus (Deiters) M = medial vestibular nucleus MLF = medial longitudinal fasciculus N.c. = cochlear nuclei N.c.p. = nucleus of the posterior commissure N.cu.e. = external cuneate nucleus

N.D. N.int. V mo V na V pr

= = = = --

RMV

= = Ru. = S and SV x = III, IV, VI XII

=

nucleus of Darkschewitsch interstitial nucleus of Cajal motor trigeminal nucleus motor trigeminal nucleus principal sensory trigeminal nucleus rostral portion of medial vestibular nucleus red nucleus superior vestibular nucleus small celled group x, lateral to descending vestibular nucleus cranial nerve nuclei hypoglossal nucleus

SUMMARY U n i l a t e r a l stereotaxic lesions were m a d e in restricted p o r t i o n s o f the cat vestibular nuclei, a n d the resulting a x o n a l d e g e n e r a t i o n was s t a i n e d b y the N a u t a 2a method. Vestibular p r o j e c t i o n s to the e x t r a o c u l a r m o t o r nuclei arise only in the s u p e r i o r v e s t i b u l a r nucleus (SV) a n d in r o s t r a l p o r t i o n s o f the m e d i a l vestibular nucleus ( R M V ) , the regions which receive the central p r o j e c t i o n s o f the semi-circular c a n a l ganglia. F i b e r s a s c e n d i n g f r o m these two regions follow s e p a r a t e courses. F r o m c a u d a l p o r t i o n s o f the SV, a few fibers pass m e d i a l l y to the ipsilateral VI nucleus. The m a j o r i t y o f a s c e n d i n g SV fibers pass r o s t r o m e d i a l l y into the ipsilateral M L F f r o m which they e n t e r the ipsilateral t r o c h l e a r a n d I I I nuclei. W i t h i n c a u d a l p o r t i o n s o f the I I I nuclei, fibers decussate a n d t u r n c a u d a l l y to d i s t r i b u t e to the c o n t r a l a t e r a l trochlear nucleus. F i b e r s p a s s i n g to the c o n t r a l a t e r a l e x t r a o c u l a r m o t o r nuclei cross the midline within the I I I nuclei. F r o m the R M V , a s c e n d i n g fibers pass m e d i a l l y into the ipsilateral VI nucleus.

Brain Research, 20 (1970) 159-179

178

E. TARLO\

The p r o j e c t i o n s from rostral p o r t i o n s o f the R M V decussate rostral to those from caudal p o r t i o n s o f the R M V . A few fibers are d i s t r i b u t e d to the contralateral VI nuclei. A s c e n d i n g fibers pass in the c o n t r a l a t e r a l M L F to the E O M nuclei bilaterally. Both the SV and R M V p r o j e c t to the interstitial nuclei o f Cajal and the nuclei o f D a r k s c h e w i t s c h ; from the SV, this p r o j e c t i o n is p r e d o m i n a n t l y ipsilateral, while from the R M V it is p r e d o m i n a n t l y c o n t r a l a t e r a l . Extensive areas o f overlap between the p r o j e c t i o n s o f the SV and R M V exist. Small regions within the SV a n d R M V have wide p r o j e c t i o n fields within the E O M nuclei. The p r o j e c t i o n fields o f restricted regions o f the SV a n d R M V are depicted in detail. This vast a n d beautiful intricacy o f o r g a n i z a t i o n p r o v i d e s direct p a t h w a y s over which a relatively few n e u r o n s within the s u p e r i o r and m e d i a l vestibular nuclei can influence the activity o f large n u m b e r s o f e x t r a o c u l a r muscle m o t o r neurons. Conversely, small g r o u p s o f e x t r a o c u l a r muscle m o t o r n e u r o n s receive p r o j e c t i o n s from large areas in the s u p e r i o r a n d m e d i a l vestibular nuclei. The delicate influences o f the vestibular system on c o o r d i n a t e d eye m o v e m e n t s must d e p e n d on such exquisite organization. ACKNOWLEDGEMENTS I t h a n k Professor A l f Brodal a n d Professor F r e d W a l b e r g for p r o v i d i n g facilities for this research, a n d Miss Evy E r i k s e n a n d Mrs. N a n t i A r n b o r g for p r e p a r i n g the histological specimens a n d the final drawings. REFERENCES l ABD-EL-MALEK, S., On the localization of nerve centres of the extrinsic ocular muscles in the

oculomotor nucleus, J. Anat. (Lond.), 72 (1938) 518-523. 2 ANGAUT, P., AND ]~RODAL, A., The projection of the 'vestibulo-cerebellum' onto the vestibular nuclei in the cat, Arch. ital. Biol., 105 (1967) 441479. 3 BENDER, M. B., AND WEINSTEIN, E. A., Functional representation in the oculomotor and trochlear nuclei, Arch. Neurol. Psychiat. (Chic.), 49 (1943) 98-106. 4 BERMAN,A. L., The Brainstem of the Cat: A Cyto-architectonic Atlas with Stereotaxic Coordinates, University of Wisconsin Press, Madison, Wisc., 1968, 175 pp. 5 BIENFANG, D. C., Location of the cell bodies of the superior rectus and inferior oblique motoneurons in the cat, Exp. Neurol., 21 (1968) 455-466.

6 BOWSHER,D., BRODAL,A., ANDWALBERG,F., The relative values of the Marchi method and some silver impregnation techniques, Brain, 83 (1958) 150-159. 7 BRODAL, A., AND POMPEIANO, O., The origin of ascending fibers of the medial longitudinal fasciculus from the vestibular nuclei. An experimental study in the cat, Acta morph, neerl.-scand., 111958) 306-328. 8 BRODAL,A., POMPEIANO,O., AND WALBERG, F., The Vestibular Nuclei and their Connections, Anatomy, and Functional Correlations, Oliver and Boyd, London, 1962, 193 pp. 9 BRODAL, A., UND TORVIK,A., ~ber den Ursprung der sekund~iren vestibulo-cerebellaren Fasern bei der Katze. Eine experimentell-anatomische Studie, Arch. Psychiat. Nervenkr., 195 (1957) 550-567. 10 BUCHANAN,A. R., The course of secondary vestibular fibers in the cat, J. comp. Neurol., 67 (1937/183-204. l l CARPENTER, M. B., AND STROMINGER, N. L., Cerebello-oculomotor fibers in the rhesus monkey, J. comp. Neurol., 123 (1964)211-230. 12 COHEN, B., SUZUKI, J. I., AND BENDER, M. B., Eye movements from semicircular canal nerve stimulation in the cat, Ann. Otol. (St. Louis), 73 (1964) 153-169. Brain Research, 20 (1970) 159-179

ORGANIZATION OF VESTIBULO-OCULOMOTOR PROJECTIONS

179

13 Dow, R. S., AND MANNI, E., The relationship of the cerebellum to extraocular movements. In M. B. BENDER(Ed.), The Oculomotor System, Hoeber, New York, 1964, pp. 280-292. 14 FERRARO, A., PACELEA, B. L., AND BARRERA, S. E., Effects of lesions of the medial vestibular nucleus. An anatomical and physiological study in macacus rhesus monkeys, J. comp. Neurol., 37 (1940) 7-36. 15 GRAY, L. P., Some experimental evidence on the connections of the vestibular mechanism in the cat, J. comp. Neurol., 41 (1926) 319-356. 16 JANSEN, J., Efferent cerebellar connections. In J. JANSEN AND A. BRODAL (Eds.), Aspects of Cerebellar Anatomy, Tanum, Oslo, 1954, pp. 189-243. 17 LADPLI, R., AND BRODAL)A., Experimental studies of commissural and reticular formation projections of the vestibular nuclei in the cat, Brain Research, 8 (1968) 65-96. 18 LORENTEDE NG, R., Vestibulo-ocular reflex arc, Arch. Neurol. Psychiat. (Chic.), 30 (1933) 245-291. 19 LORENTE DE NG, R., Anatomy of the eighth nerve. The central projection of the nerve endings of the internal ear, Laryngoscope (St. Louis), 43 (1933) 1-38. 20 MCMASTERS, R. E., WEISS, A. H., AND CARPENTER, M. B., Vestibular projections to the nuclei of the extraocular muscles, Amer. J. Anat., 118 (1966) 163-194. 21 MARKHAM, C. H., Midbrain and contralateral labyrinth influences on brain stem vestibular neurons in cat, Brain Research, 9 (1968) 312-333. 22 MARKHAM,C. H., PRECHT, W., AND SHIMAZU,H., Effect of stimulation of interstitial nucleus of Cajal on vestibular unit activity in cat, J. Neurophysiol., 29 (1966) 493-507. 23 NAUTA,W. J. H., Silver impregnation of degenerating axons. In W. F. WINDLE (Ed.), New Research Techniques of Neuroanatomy, Thomas, Springfield, Ill., 1957, pp. 17-26. 24 NYBERG=HANSEN,R., Origin and termination of fibers from the vestibular nuclei descending in the medial longitudinal fasciculus. An experimental study with silver impregnation methods in the cat, J. comp. Neurol., 122 (1964) 355-367. 25 POMPEIANO,O., AND WALBERG, F., Descending connections to the vestibular nuclei in the cat, J. comp. Neurol., 108 (1958) 465-503. 26 RASMUSSEN,A. T., Secondary vestibular fibers in the cat, J. comp. Neurol., 54 (1932) 143-171. 27 SCH~IaEL, A., MARKHAM, C. H., AND KOEGLER, R., Neural correlates of the vestibulo-ocular reflex, Neurology (Minneap.), 11 (1961) 1055-1065. 28 SHIMAZU,H., AND PRECHT, W., Inhibition of central vestibular neurons from the contralateral labyrinth and its mediating pathway, J. Neurophysiol., 29 (1966) 467-492. 29 SNIDER, R. S., AND NIEMER, W. T., A Stereotaxic Atlas of the Cat Brain, University of Chicago Press, Chicago, Ill., 1961. 30 STEIN, B. M., AND CARPENTER, M. B., Central projections of the vestibular ganglia innervating specific parts of the labyrinth in the rhesus monkey, Amer. J. Anat., 120 0967) 281-318. 31 SZENT.~GOTHAI,J., Die zentrale Innervation der Augenbewegungen, Arch. Psychiat. Nervenkr., 116 (1943) 721-760. 32 SZENT.~GOTHAI,J., The elementary vestibulo-ocular reflex arc, J. Neurophysiol., 13 (1950) 395-407. 33 SZENT.~.GOTHAI,J., Pathways and synaptic articulation patterns connecting vestibular receptors and oculomotor nuclei. In M. B. BENDER (Ed.), The Oculomotor System, Hoeber, New York, N.Y., 1964, pp. 205-223. 34 TARLOV, E., The rostral projections of the primate vestibular nuclei: an experimental study in macaque, baboon and chimpanzee, J. comp. Neurol., 135 (1969) 27-56. 35 WALBERG,F., The early changes in degenerating boutons and the problem of argyrophilia. Light and electron microscopical observations, J. comp. Neurol., 122 (1964) 113-137. 36 WALBERG, F., Morphological correlates of postsynaptic inhibitory processes. In Wenner-Gren Center International Symposium Series, Vol. 10, Pergamon, New York, N.Y., 1968, pp. 7-41. 37 WALBERG, F., BOWSHER, D., AND BRODAL, A., The termination of primary vestibular fibers in the vestibular nuclei in the cat. An experimental study with silver methods, J. comp. Neurol., 110 (1958) 391-419. 38 WARWICK,R., Representation of the extra-ocular muscles in the oculomotor nuclei of the monkey, J. comp. Neurol., 98 (1953) 449-504. 39 WILSON,V. J., WYLIE, R. M., AND MARCO, L. A., Organization of the medial vestibular nucleus, J. Neurophysiol., 31 (1968) 166-175. 40 WILSON,V. J., WYLIE, R. M., AND MARCO, L. A., Synaptic inputs to cells in the medial vestibular nucleus, J. Neurophysiol., 31 (1968) 176-185. 41 GACEK, R., The course and central termination of first order neurons supplying vestibular end organs in the cat, Acta oto-laryng. (Stockh.), Suppl. 254 0969) 1-66.

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