Ann Otol 88 :1979
VESTIBULAR NEUROANATOMY RECENT OBSERVAnONS RICHARD
R.
GACEK,
MD
SYRACUSE, NEW YORK
The modern neuroanatomical technique of using a retrograde axoplasmic tracer (horseradish peroxidase) to label neurons has aided the revelation of several important connections in the vestibular system. The organization of the oculomotor nucleus and the existence of an interneuron in the abducens nucleus have importance in understanding some ocular disorders. A detailed description of the location of vestibule-ocular neurons to individual extraocular muscles is now available which may provide a basis for understanding how these reflexes function normally and abnormally. Interconnections between the vestibular nuclei are provided by commissural neurons located in the superior, medial and group Y nuclei. These projections are probably of importance in vestibular compensation. A possible hypothesis of vestibular hair cell projection suggests that type I cells project over vestibulo-ocular neurons while type II cells project over commissural pathways.
Prior to 1971 neuroanatomical connections in the central and peripheral nervous system were demonstrated primarily by anterograde fiber degeneration teclmiques and the retrograde cell change method.':" These techniques made possible the observation of many anatomical projections in the vestibular pathway. Although the anterograde teclmique has been useful in demonstrating the course and termination of long fiber tracts, the retrograde cell method was significantly limited in its ability to clearly and consistently demonstrate the cell origins of such fiber pathways. Other techniques such as autoradiography require sophisticated methodology and are often difficult to interpret because of background activity. The demonstration that tracers could be carried by retrograde axoplasmic flow over long distances to the cell body of motor neurons ushered in a new era in neuroanatomical investigation.v" This technique has been used to identify many of the second and third order neurons in the vestibular system. In the central vestibular pathways, the greatest contribution from a careful application of this technique has been the demonstration of the organization of nuclear masses. The extraocular nuclei and the vestibular nuclei have been studied in-
tensively in our laboratory because of their importance in the vestibulo-ocular reflex. This report will summarize some of the new neuroanatomical connections revealed by this method over the past seven years and suggest their significance in the clinical evaluation of the vestibular system. EXTRAOCULAR NUCLEI: OCULOMOTOR NUCLEUS (III)
The oculomotor or third nerve nucleus is the most complex of the extraocular nuclei since it contains the motor neurons which innervate four eye muscles. These are superior, inferior and medial recti and inferior oblique muscles. The past uncertainty regarding the location of motor neuron groups in this nucleus was due mainly to the difficulty in obtaining clear-cut changes in small cells with the retrograde cell change method. The use of horseradish peroxidase (HRP) as a tracer injected into the individual extraocular muscles of the kitten has revealed an orderly arrangement of neuron groups in the oculomotor nucleus." The model in Figure 1 shows that the subgroups of the third nerve nucleus are arranged as discrete nuclear masses with two located in the rostral half of the nucleus and two in the caudal half. The subgroups for the medial and inferior recti are oriented dorsoventrally
From the Department of Otolaryngology, Upstate Medical Center, Syracuse, New York. This study was supported by USPH grant No. NS 08451, NINCDS, NIH, Bethesda. Maryland. Presented at the meeting of the American Otological Society, Tnc., Los Angeles, California, March 31-Aprll I, 1979.
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Caudal Central Nucleus
IR
Fig. 1. Drawing of a model of the oculomotor nucleus viewed from above showing the organization into subgroups supplying extraocular muscles. SR - Superior rectus; IR - Inferior rectus; 10 - Inferior oblique; MR - Medial rectus.
in the rostral half of the nucleus while the superior rectus and inferior oblique subgroups comprise the caudal half. This arrangement indicates that it is possible to obtain an isolated paresis of individual eye muscles following a central vascular lesion involving a particular subgroup. This model also serves as a guide for neuroanatomical experiments which are designed to locate the position of the vestibulo-ocular (VO) neurons projecting to each of these subgroups. A particularly interesting connection has been demonstrated between the abducens and the oculomotor nuclei. Suggestive evidence of such an interneuron was observed when a consistent number
of unlabelled cells were seen in the abducens nucleus following the injection of large amounts of tracer to the lateral rectus muscle." This observation indicated that these unlabelled neurons projected to a location other than to the lateral rectus muscle. Confirmation of a different termination for these abducens neurons was made when the injection of tracer into the medial rectus subgroup of the oculomotor nucleus consistently labelled neurons contralaterally in the abducens nucleus' (Fig. 2). These experiments established an interneuron located in the abducens nucleus which projects contralaterally to the medial rectus subgroup (Fig. 3). It is this interneuron which has been implicated in the syndrome of anterior internuclear ophthalmoplegia, a neuroophthalmologic finding in demyelinating disorders such as multiple sclerosis. This syndrome consists of a disturbance in conjugate eye movements where the contralateral eye fails to adduct with abduction of the ipsilateral eye but adduction bilaterally is preserved on convergence. The demyelinating process presumably affects the axons of this interneuron during its
Fig. 2. Dark field photomicrograph showing labelled interneurons (arrows) in the contralateral abducens nucleus following injection of HRP into the medial rectus subgroup. 7 - Facial nerve; MLF - Medial longitudinal fasciculus.
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MR ill ATD MLF
IFe
Fig. 4. Drawing of the VO pathways for vertical and oblique eye movoments. BC - Brachium conjunctivum; IFC - Infracerebellar nucleus; S - Superior vestibular nucleus; L - Lateral vestibular nucleus; M - Medial vestibular nucleus; D Descending vestibular nucleus. Fig. 3. Drawing summarizing the vestibulo-ocular pathways for horizontal eye movements. MR - Medial rectus subnucleus; ATD - Ascending tract of Deiters; MLF - Medial longitudinal fasciculus; NPH - Nucleus prepositius hypoglossi.
course in the medial longitudinal fasciculus (MLF). VESTIBULAR NUCLEI: VESTIBULOOCULAR REFLEX (VOR)
Several new observations in the neural projections for VOR have been revealed by the HRP tracer technique. Utilizing small injections of tracer into the sixth, fourth and subgroups of the third nucleus, neurons in the vestibular nuclei which activate these eye muscles have been identified." The location and type of vestibula-ocular neurons have been determined which may have significant clinical implications. The activation of these vestibuleocular neurons is dependent on the termination of first order vestibular neurons in the vestibular nuclei.' Neuron degeneration studies have shown that canal afferents terminate mainly in the superior and medial nuclei but also in the lateral nucleus to a smaller degree. Utricular afferents end in the lateral nucleus (ventral portion), and the rostral parts of the medial nucleus. The saccular afferents terminate in the lateral, medial and group Y nuclei. The nearby infracerebellar nucleus probably also receives an input from the saccule," Vesti-
bulo-ocular reflexes are, therefore, particularly important for semicircular canal function, less so for utricular activity and least for the role of the saccule. The VO neurons which project to eye muscles serving horizontal movements (medial rectus and lateral rectus) are located almost entirely within the medial vestibular nucleus" (Fig. 3). Furthermore, these neurons are concentrated in the rostral part of the medial nucleus where the dorsal acoustic stria penetrates this nucleus. Most of these neurons project directly to the nearby abducens nuclei while some combine with cells in the lateral nucleus to form the ascending tract of Deiters, which reaches the ipsilateral medial rectus subgroup. This tract courses lateral to the MLF and is, therefore, remote from the vicinity of the fourth ventricle. The abducens interneuron completes the neuronal circuitry for horizontal movements by forming a link between the lateral rectus and contralateral medial rectus. Those vestibular nuclear neurons which supply the eye muscles responsible for vertical and oblique movements (superior and inferior recti, superior and inferior oblique) are far more numerous than those responsible for horizontal movements, and are located in both the superior and medial vestibular nuclei as well as the infracere-
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Fig. 5. Dark field demonstration of labelling in the A) Infracerebellar nucleus foling injection of the third nucleus with tracer; B) Group Y nucleus following injection of the contralateral Y nucleus with tracer. L - Lateral vestibular nucleus; R - Restiform body; IFC - Infracerebellar nucleus.
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bellar nuoleus'" (Fig. 4). The contralateral MLF pathway arises from the caudal region of the medial nucleus while the cells forming the ipsilateral MLF tract are located in the superior vestibular nucleus. Additional va neurons to these eye muscles are located in dorsal portions of the superior nuclei and project bilaterally to the third and fourth nuclei by way of the brachium conjunctivum. Furthermore, the infracerebellar nucleus which is near the group Y nucleus (Fig. 5) provides a vestibulo-ocular linkage with the third and fourth nuclei from its peripheral input, the saccule. The va neurons in this nucleus also reach the extraocular neurons by way of the brachium conjunctivum. The difference in location, number, and projection pathways of va neurons for horizontal ocular movements and those activating vertical and oblique movements (Figs. 3 and 4) offer a credible explanation for the perversion of invoked caloric nystagmus in cases with fourth ventricle neoplasms or cerebellar cysts. It is likely that the superficial location of abducens va neurons in the medial vestibular nucleus renders them vulnerable to compression by tumors which extend to the fourth ventricle floor. Elimination of these abducens va neurons would impair horizontal eye movement. It is less likely that the compressive effect of such tumors is directly upon the abducens nucleus which is protected by the overlying facial nerve at its first genu. On the other hand the va linkages for vertical and oblique eye movements are far more numerous, are remotely located in the superior and infracerebellar nuclei, and travel over fiber tracts (rostral medial longitudinal fasciculus, brachium conjunctivum) that are protected from pressure in the fourth ventricle. Invoked nystagmus from caloric stimulation of the lateral canal in such cases of fourth ventricle tumor would, therefore, be manifested by a vertical and oblique nystagmus rather than the expected horizontal nystagmus. A substantial group of small neurons kno,,:n as the nucleus prepositus hypoglOSSI have been shown to be involved in vestibulo-ocular reflexes. to Tracer experiments have demonstrated conclu-
671
Fig. 6. Drawing of the commissural connections between the vestibular nuclei. Y - Group Y nucleus.
sively that these small numerous cells project to all of the extraocular nuclei. Physiological studies have confirmed that they exert an effect on motor neurons to the eye muscles. Their precise role in the VOR, however, is not clear at this time. VESTIBULOVESTIBULAR (COMMISSURAL) CONNECTIONS OF VESTIBULAR NUCLEI
The tracer method has demonstrated that the commissural neurons are located primarily in the superior, medial vestibular nuclei and group Y nuclei>' (Fig. 6). These commissural neurons are small and very numerous. They are predominantly located in the peripheral areas of the superior nucleus and the rostral extension of the medial nucleus (Fig. 7), and terminate in the superior and medial nuclei of the contralateral side. The group Y nucleus which receives peripheral input from the saccule is purely commissural (Fig. 5) and projects transversely at the rostral level of the superior vestibular nuclei to terminate presumably in the contralateral Y nucleus. The commissural projections are probably of significance in the compensatory mechanism which the vestibular system utilizes following unilateral ablation of the labyrinth. A characteristic feature of the vestibular nuclei is that those nuclei which serve both vestibulo-ocular and commissural functions are populated by large and small neurons. In the superior nucleus, the large cells occupy the central area of the nucleus while the small cells are located peripherally in the nucleus ( Fig. 8A). The rostral extension of the medial nucleus has small cells filling the nucleus with the large neurons
·Gacek RR: Location of trochlear vestibulo-ocular neurons In the cat. Unpublished data.
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_i&\
Fig. 7. Dark field view of the medial vestibular nucleus with labelled commissural neurons following placement of tracer in the contralateral vestibular nuclei. Most of the neurons in this part of the nucleus are commissural. Compare to Fig. 8B. DAS - Dorsal acoustic stria; 4 - Fourth ventricle.
located ventrally and somewhat scattered among the small ones (Fig. 8B). Group Y is made up entirely of small cells but is capped dorsally by the infracerebellar nucleus which has larger neurons that project to the third and fourth nuclei and are responsible for vestibuloocular connections. The more numerous small neurons in the superior, medial and group Y nuclei are responsible for the commissural projections. TERMINATION OF TYPE I AND TYPE II VESTIBULAR HAIR CELLS
An enlarging collection of data now suggests that the type I and type II hair cells in the vestibular end-organs, particularly the cristae, project over different first order neurons to separate locations within the vestibular nuclei. The type I hair cells are innervated by large caliber first order neurons which terminate on the large second order neurons located in the central portion of the superior vestibular nucleus.' They serve vestibulo-ocular reflexes." The type II
hair cells innervated by small caliber afferent neurons project to the peripheral zones of the superior nucleus where contact is made primarily with small neurons.' It is also possible that some contact with large vestibulo-ocular neurons may be made by these small afferents. These anatomical correlates have been supported by physiological observations that the spontaneous electrical activity in these two types of afferent neurons is different with the large afferents displaying an irregular spontaneous discharge pattern while the small afferents have a regular discharge pattem.v> An attractive hypothesis holds that the type I and type II hair cells of the cristae project via different first order neurons to those regions of the superior vestibular nucleus where separate second order neuron projections are formed. Type I hair cell activity is projected to the extraocular nuclei while the type II hair function is mediated commissurally (Fig. 9). The hypothesis can be used to explain
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Fig. 8. Photo of the neuron types in the A) superior and B) rostral medial nucleus as demonstrated by the thionine technique. The large neurons in both nuclei are vestibulo-ocular while the small cells are commissural. 4 - Fourth ventricle.
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vv
[J
Fig. 9. Drawing of the hypothesized central connections of type I and II hair cells in the cristae. VO - Vestibulo-ocular neurons; VV - Vestibulovestibular connection.
some clinical situations. 1) When streptomycin has been used to ablate peripheral vestibular function, abolition of the vestibula-ocular reflex to ice water stimulus is used to indicate the end point. Histological examination of vestibular end-organs after this effect in the laboratory animal reveals that all type I hair cells are degenerated but that type II hair cells remain. In streptomycin-ablated human patients treated for bilateral Meniere's disease where caloric function has been abolished by the use of this antibiotic, the patients often retain better equilibrium than if bilateral surgical destruction of the labyrinths was carried out. Although it is probable that the otolith organs are partly responsible for some of this resid-
ual vestibular function, it is also possible that the commissural function mediated by remaining type II hair cells may be responsible. 2) It has been observed clinically that loss of the vestibulo-ocular reflex is not an accurate evaluation of the presence or absence of function in a labyrinth. This is exemplified by those patients who have lost all response to ice water caloric stimulation but continue to have a significant vestibular disturbance. When these patients with unilateral ear disease are subjected to complete surgical ablation, they experience an immediate postoperative vestibular disequilibrium indicating a recent loss of vestibular function, but eventually recover and are relieved of their preoperative vestibular symptoms. This course of events suggests that some functional component in the vestibular sense organs, especially the cristae, has been ablated, and was probably responsible for the vestibular disturbance. The number of anatomical connections revealed by the HRP tracer method has been increasing steadily over recent years. The clinical and research significance of these observations have been discussed in this report. A more sophisticated use of the tracer technique is now being employed to localize precisely the point to point projection of neurons within the vestibular system. Only after a complete detailed description of the vestibular system has been achieved can we logically approach vestibular function and dysfunction.
REFERENCES 1. Gacek RR: The course and central termination of first order neurons supplying vestibular end organs in the cat. Acta Otolaryngol (Stockh) [Suppl 254:1-661 1969 2. Gacek RR: Anatomical demonstration of the vestibulo-ocular projections in the cat. Acta Otolaryngol (Stockh) [Suppl 293: 1-63] 1971 3. Tarlov E: Organization of vestibulooculomotor connections in the cat. Brain Res 20:159-179, 1970 4. Kristensson K, Olsson Y: Retrograde axonal transport of protein. Brain Res 29:363365, 1971 5. Kristensson K, Olsson Y, Sjostrand J: Axonal uptake and retrograde transport of exogenous proteins in the hypoglossal nerve. Brain Res 32:399, 1971 6. Gacek RR: Localization of neurons sup-
plying the extra ocular muscles in the kitten using horseradish peroxidase. Exp Neurol 44: 381-403, 1974 7. Gacek RR: Location of brain stem neurons projecting to the oculomotor nucleus in the cat. Exp Neurol 57:725-749, 1977 8. Gacek RR: Afferent and efferent vestibular system. Morphological Aspects. Neuroscience Satellite Symposium on the Vestibular, Pittsburgh, PA, Nov 1-3, 1978 9. Gacek RR: Location of abducens afferent neurons in the cat. Exp Neurol, in press 10. Baker R, Berthoz A: Is the praepositus hypoglossi nucleus the source of another vestibulo-ocular pathway? Brain Res 86: 121-127, 1975 11. Gacek RR: Location of commissural neurons in the vestibular nuclei of the cat. Exp Neurol 59:479-491, 1978
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canals of the squirrel monkey. III. Variations among units in their discharge properties. J Neurophysiol 34:676-684, 1971 14. Walsh BT, Miller JB, Gacek RR, et al: Spontaneous activity in the eighth cranial nerve of the cat. Intern J Neurosci 3:221-236, 1972
12. Goldberg JM, Fernandez C: Physiology of peripheral neurons innervating semicircular canals of the squirrel monkey. I. Resting discharge and response to constant angular accelerations. J Neurophysiol 34:635-660, 1971 13. Coldberg JM, Fernandez C: Physiology of peripheral neurons innervating semicircular
REPIUNTS - Richard R. Gacek, MD, Department of Otolaryngology, Upstate Medical Center, Syracuse, NY 13210.
,..., ,...,
CALL FOR PAPERS OTO-RHINO-LARYNGOLOGICAL RESEARCH SOCIETY The next two meetings of the O.R.S. will be held as follows: April 11, 1980 at the University of Bristol: October 3, 1980 at the Royal National Throat, Nose and Ear Hospital, Gray's Inn Road, London. Those wishing to read a paper should submit an abstract (10 copies with the name and address on the top copy only) of not more than 250 words to the following: Professor P. Stell, ChM, FRCS, Secretary, Dept. of Otolaryngology, Royal Liverpool Hospital, Prescot Street, Liverpool. L7 8XP.
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VESTIBULAR NEUROANATOMY RECENT OBSERVAnONS RICHARD
R.
GACEK,
MD
SYRACUSE, NEW YORK
The modern neuroanatomical technique of using a retrograde axoplasmic tracer (horseradish peroxidase) to label neurons has aided the revelation of several important connections in the vestibular system. The organization of the oculomotor nucleus and the existence of an interneuron in the abducens nucleus have importance in understanding some ocular disorders. A detailed description of the location of vestibule-ocular neurons to individual extraocular muscles is now available which may provide a basis for understanding how these reflexes function normally and abnormally. Interconnections between the vestibular nuclei are provided by commissural neurons located in the superior, medial and group Y nuclei. These projections are probably of importance in vestibular compensation. A possible hypothesis of vestibular hair cell projection suggests that type I cells project over vestibulo-ocular neurons while type II cells project over commissural pathways.
Prior to 1971 neuroanatomical connections in the central and peripheral nervous system were demonstrated primarily by anterograde fiber degeneration teclmiques and the retrograde cell change method.':" These techniques made possible the observation of many anatomical projections in the vestibular pathway. Although the anterograde teclmique has been useful in demonstrating the course and termination of long fiber tracts, the retrograde cell method was significantly limited in its ability to clearly and consistently demonstrate the cell origins of such fiber pathways. Other techniques such as autoradiography require sophisticated methodology and are often difficult to interpret because of background activity. The demonstration that tracers could be carried by retrograde axoplasmic flow over long distances to the cell body of motor neurons ushered in a new era in neuroanatomical investigation.v" This technique has been used to identify many of the second and third order neurons in the vestibular system. In the central vestibular pathways, the greatest contribution from a careful application of this technique has been the demonstration of the organization of nuclear masses. The extraocular nuclei and the vestibular nuclei have been studied in-
tensively in our laboratory because of their importance in the vestibulo-ocular reflex. This report will summarize some of the new neuroanatomical connections revealed by this method over the past seven years and suggest their significance in the clinical evaluation of the vestibular system. EXTRAOCULAR NUCLEI: OCULOMOTOR NUCLEUS (III)
The oculomotor or third nerve nucleus is the most complex of the extraocular nuclei since it contains the motor neurons which innervate four eye muscles. These are superior, inferior and medial recti and inferior oblique muscles. The past uncertainty regarding the location of motor neuron groups in this nucleus was due mainly to the difficulty in obtaining clear-cut changes in small cells with the retrograde cell change method. The use of horseradish peroxidase (HRP) as a tracer injected into the individual extraocular muscles of the kitten has revealed an orderly arrangement of neuron groups in the oculomotor nucleus." The model in Figure 1 shows that the subgroups of the third nerve nucleus are arranged as discrete nuclear masses with two located in the rostral half of the nucleus and two in the caudal half. The subgroups for the medial and inferior recti are oriented dorsoventrally
From the Department of Otolaryngology, Upstate Medical Center, Syracuse, New York. This study was supported by USPH grant No. NS 08451, NINCDS, NIH, Bethesda. Maryland. Presented at the meeting of the American Otological Society, Tnc., Los Angeles, California, March 31-Aprll I, 1979.
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Caudal Central Nucleus
IR
Fig. 1. Drawing of a model of the oculomotor nucleus viewed from above showing the organization into subgroups supplying extraocular muscles. SR - Superior rectus; IR - Inferior rectus; 10 - Inferior oblique; MR - Medial rectus.
in the rostral half of the nucleus while the superior rectus and inferior oblique subgroups comprise the caudal half. This arrangement indicates that it is possible to obtain an isolated paresis of individual eye muscles following a central vascular lesion involving a particular subgroup. This model also serves as a guide for neuroanatomical experiments which are designed to locate the position of the vestibulo-ocular (VO) neurons projecting to each of these subgroups. A particularly interesting connection has been demonstrated between the abducens and the oculomotor nuclei. Suggestive evidence of such an interneuron was observed when a consistent number
of unlabelled cells were seen in the abducens nucleus following the injection of large amounts of tracer to the lateral rectus muscle." This observation indicated that these unlabelled neurons projected to a location other than to the lateral rectus muscle. Confirmation of a different termination for these abducens neurons was made when the injection of tracer into the medial rectus subgroup of the oculomotor nucleus consistently labelled neurons contralaterally in the abducens nucleus' (Fig. 2). These experiments established an interneuron located in the abducens nucleus which projects contralaterally to the medial rectus subgroup (Fig. 3). It is this interneuron which has been implicated in the syndrome of anterior internuclear ophthalmoplegia, a neuroophthalmologic finding in demyelinating disorders such as multiple sclerosis. This syndrome consists of a disturbance in conjugate eye movements where the contralateral eye fails to adduct with abduction of the ipsilateral eye but adduction bilaterally is preserved on convergence. The demyelinating process presumably affects the axons of this interneuron during its
Fig. 2. Dark field photomicrograph showing labelled interneurons (arrows) in the contralateral abducens nucleus following injection of HRP into the medial rectus subgroup. 7 - Facial nerve; MLF - Medial longitudinal fasciculus.
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MR ill ATD MLF
IFe
Fig. 4. Drawing of the VO pathways for vertical and oblique eye movoments. BC - Brachium conjunctivum; IFC - Infracerebellar nucleus; S - Superior vestibular nucleus; L - Lateral vestibular nucleus; M - Medial vestibular nucleus; D Descending vestibular nucleus. Fig. 3. Drawing summarizing the vestibulo-ocular pathways for horizontal eye movements. MR - Medial rectus subnucleus; ATD - Ascending tract of Deiters; MLF - Medial longitudinal fasciculus; NPH - Nucleus prepositius hypoglossi.
course in the medial longitudinal fasciculus (MLF). VESTIBULAR NUCLEI: VESTIBULOOCULAR REFLEX (VOR)
Several new observations in the neural projections for VOR have been revealed by the HRP tracer technique. Utilizing small injections of tracer into the sixth, fourth and subgroups of the third nucleus, neurons in the vestibular nuclei which activate these eye muscles have been identified." The location and type of vestibula-ocular neurons have been determined which may have significant clinical implications. The activation of these vestibuleocular neurons is dependent on the termination of first order vestibular neurons in the vestibular nuclei.' Neuron degeneration studies have shown that canal afferents terminate mainly in the superior and medial nuclei but also in the lateral nucleus to a smaller degree. Utricular afferents end in the lateral nucleus (ventral portion), and the rostral parts of the medial nucleus. The saccular afferents terminate in the lateral, medial and group Y nuclei. The nearby infracerebellar nucleus probably also receives an input from the saccule," Vesti-
bulo-ocular reflexes are, therefore, particularly important for semicircular canal function, less so for utricular activity and least for the role of the saccule. The VO neurons which project to eye muscles serving horizontal movements (medial rectus and lateral rectus) are located almost entirely within the medial vestibular nucleus" (Fig. 3). Furthermore, these neurons are concentrated in the rostral part of the medial nucleus where the dorsal acoustic stria penetrates this nucleus. Most of these neurons project directly to the nearby abducens nuclei while some combine with cells in the lateral nucleus to form the ascending tract of Deiters, which reaches the ipsilateral medial rectus subgroup. This tract courses lateral to the MLF and is, therefore, remote from the vicinity of the fourth ventricle. The abducens interneuron completes the neuronal circuitry for horizontal movements by forming a link between the lateral rectus and contralateral medial rectus. Those vestibular nuclear neurons which supply the eye muscles responsible for vertical and oblique movements (superior and inferior recti, superior and inferior oblique) are far more numerous than those responsible for horizontal movements, and are located in both the superior and medial vestibular nuclei as well as the infracere-
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Fig. 5. Dark field demonstration of labelling in the A) Infracerebellar nucleus foling injection of the third nucleus with tracer; B) Group Y nucleus following injection of the contralateral Y nucleus with tracer. L - Lateral vestibular nucleus; R - Restiform body; IFC - Infracerebellar nucleus.
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bellar nuoleus'" (Fig. 4). The contralateral MLF pathway arises from the caudal region of the medial nucleus while the cells forming the ipsilateral MLF tract are located in the superior vestibular nucleus. Additional va neurons to these eye muscles are located in dorsal portions of the superior nuclei and project bilaterally to the third and fourth nuclei by way of the brachium conjunctivum. Furthermore, the infracerebellar nucleus which is near the group Y nucleus (Fig. 5) provides a vestibulo-ocular linkage with the third and fourth nuclei from its peripheral input, the saccule. The va neurons in this nucleus also reach the extraocular neurons by way of the brachium conjunctivum. The difference in location, number, and projection pathways of va neurons for horizontal ocular movements and those activating vertical and oblique movements (Figs. 3 and 4) offer a credible explanation for the perversion of invoked caloric nystagmus in cases with fourth ventricle neoplasms or cerebellar cysts. It is likely that the superficial location of abducens va neurons in the medial vestibular nucleus renders them vulnerable to compression by tumors which extend to the fourth ventricle floor. Elimination of these abducens va neurons would impair horizontal eye movement. It is less likely that the compressive effect of such tumors is directly upon the abducens nucleus which is protected by the overlying facial nerve at its first genu. On the other hand the va linkages for vertical and oblique eye movements are far more numerous, are remotely located in the superior and infracerebellar nuclei, and travel over fiber tracts (rostral medial longitudinal fasciculus, brachium conjunctivum) that are protected from pressure in the fourth ventricle. Invoked nystagmus from caloric stimulation of the lateral canal in such cases of fourth ventricle tumor would, therefore, be manifested by a vertical and oblique nystagmus rather than the expected horizontal nystagmus. A substantial group of small neurons kno,,:n as the nucleus prepositus hypoglOSSI have been shown to be involved in vestibulo-ocular reflexes. to Tracer experiments have demonstrated conclu-
671
Fig. 6. Drawing of the commissural connections between the vestibular nuclei. Y - Group Y nucleus.
sively that these small numerous cells project to all of the extraocular nuclei. Physiological studies have confirmed that they exert an effect on motor neurons to the eye muscles. Their precise role in the VOR, however, is not clear at this time. VESTIBULOVESTIBULAR (COMMISSURAL) CONNECTIONS OF VESTIBULAR NUCLEI
The tracer method has demonstrated that the commissural neurons are located primarily in the superior, medial vestibular nuclei and group Y nuclei>' (Fig. 6). These commissural neurons are small and very numerous. They are predominantly located in the peripheral areas of the superior nucleus and the rostral extension of the medial nucleus (Fig. 7), and terminate in the superior and medial nuclei of the contralateral side. The group Y nucleus which receives peripheral input from the saccule is purely commissural (Fig. 5) and projects transversely at the rostral level of the superior vestibular nuclei to terminate presumably in the contralateral Y nucleus. The commissural projections are probably of significance in the compensatory mechanism which the vestibular system utilizes following unilateral ablation of the labyrinth. A characteristic feature of the vestibular nuclei is that those nuclei which serve both vestibulo-ocular and commissural functions are populated by large and small neurons. In the superior nucleus, the large cells occupy the central area of the nucleus while the small cells are located peripherally in the nucleus ( Fig. 8A). The rostral extension of the medial nucleus has small cells filling the nucleus with the large neurons
·Gacek RR: Location of trochlear vestibulo-ocular neurons In the cat. Unpublished data.
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Fig. 7. Dark field view of the medial vestibular nucleus with labelled commissural neurons following placement of tracer in the contralateral vestibular nuclei. Most of the neurons in this part of the nucleus are commissural. Compare to Fig. 8B. DAS - Dorsal acoustic stria; 4 - Fourth ventricle.
located ventrally and somewhat scattered among the small ones (Fig. 8B). Group Y is made up entirely of small cells but is capped dorsally by the infracerebellar nucleus which has larger neurons that project to the third and fourth nuclei and are responsible for vestibuloocular connections. The more numerous small neurons in the superior, medial and group Y nuclei are responsible for the commissural projections. TERMINATION OF TYPE I AND TYPE II VESTIBULAR HAIR CELLS
An enlarging collection of data now suggests that the type I and type II hair cells in the vestibular end-organs, particularly the cristae, project over different first order neurons to separate locations within the vestibular nuclei. The type I hair cells are innervated by large caliber first order neurons which terminate on the large second order neurons located in the central portion of the superior vestibular nucleus.' They serve vestibulo-ocular reflexes." The type II
hair cells innervated by small caliber afferent neurons project to the peripheral zones of the superior nucleus where contact is made primarily with small neurons.' It is also possible that some contact with large vestibulo-ocular neurons may be made by these small afferents. These anatomical correlates have been supported by physiological observations that the spontaneous electrical activity in these two types of afferent neurons is different with the large afferents displaying an irregular spontaneous discharge pattern while the small afferents have a regular discharge pattem.v> An attractive hypothesis holds that the type I and type II hair cells of the cristae project via different first order neurons to those regions of the superior vestibular nucleus where separate second order neuron projections are formed. Type I hair cell activity is projected to the extraocular nuclei while the type II hair function is mediated commissurally (Fig. 9). The hypothesis can be used to explain
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Fig. 8. Photo of the neuron types in the A) superior and B) rostral medial nucleus as demonstrated by the thionine technique. The large neurons in both nuclei are vestibulo-ocular while the small cells are commissural. 4 - Fourth ventricle.
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RICHARD R. GACEK
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Fig. 9. Drawing of the hypothesized central connections of type I and II hair cells in the cristae. VO - Vestibulo-ocular neurons; VV - Vestibulovestibular connection.
some clinical situations. 1) When streptomycin has been used to ablate peripheral vestibular function, abolition of the vestibula-ocular reflex to ice water stimulus is used to indicate the end point. Histological examination of vestibular end-organs after this effect in the laboratory animal reveals that all type I hair cells are degenerated but that type II hair cells remain. In streptomycin-ablated human patients treated for bilateral Meniere's disease where caloric function has been abolished by the use of this antibiotic, the patients often retain better equilibrium than if bilateral surgical destruction of the labyrinths was carried out. Although it is probable that the otolith organs are partly responsible for some of this resid-
ual vestibular function, it is also possible that the commissural function mediated by remaining type II hair cells may be responsible. 2) It has been observed clinically that loss of the vestibulo-ocular reflex is not an accurate evaluation of the presence or absence of function in a labyrinth. This is exemplified by those patients who have lost all response to ice water caloric stimulation but continue to have a significant vestibular disturbance. When these patients with unilateral ear disease are subjected to complete surgical ablation, they experience an immediate postoperative vestibular disequilibrium indicating a recent loss of vestibular function, but eventually recover and are relieved of their preoperative vestibular symptoms. This course of events suggests that some functional component in the vestibular sense organs, especially the cristae, has been ablated, and was probably responsible for the vestibular disturbance. The number of anatomical connections revealed by the HRP tracer method has been increasing steadily over recent years. The clinical and research significance of these observations have been discussed in this report. A more sophisticated use of the tracer technique is now being employed to localize precisely the point to point projection of neurons within the vestibular system. Only after a complete detailed description of the vestibular system has been achieved can we logically approach vestibular function and dysfunction.
REFERENCES 1. Gacek RR: The course and central termination of first order neurons supplying vestibular end organs in the cat. Acta Otolaryngol (Stockh) [Suppl 254:1-661 1969 2. Gacek RR: Anatomical demonstration of the vestibulo-ocular projections in the cat. Acta Otolaryngol (Stockh) [Suppl 293: 1-63] 1971 3. Tarlov E: Organization of vestibulooculomotor connections in the cat. Brain Res 20:159-179, 1970 4. Kristensson K, Olsson Y: Retrograde axonal transport of protein. Brain Res 29:363365, 1971 5. Kristensson K, Olsson Y, Sjostrand J: Axonal uptake and retrograde transport of exogenous proteins in the hypoglossal nerve. Brain Res 32:399, 1971 6. Gacek RR: Localization of neurons sup-
plying the extra ocular muscles in the kitten using horseradish peroxidase. Exp Neurol 44: 381-403, 1974 7. Gacek RR: Location of brain stem neurons projecting to the oculomotor nucleus in the cat. Exp Neurol 57:725-749, 1977 8. Gacek RR: Afferent and efferent vestibular system. Morphological Aspects. Neuroscience Satellite Symposium on the Vestibular, Pittsburgh, PA, Nov 1-3, 1978 9. Gacek RR: Location of abducens afferent neurons in the cat. Exp Neurol, in press 10. Baker R, Berthoz A: Is the praepositus hypoglossi nucleus the source of another vestibulo-ocular pathway? Brain Res 86: 121-127, 1975 11. Gacek RR: Location of commissural neurons in the vestibular nuclei of the cat. Exp Neurol 59:479-491, 1978
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canals of the squirrel monkey. III. Variations among units in their discharge properties. J Neurophysiol 34:676-684, 1971 14. Walsh BT, Miller JB, Gacek RR, et al: Spontaneous activity in the eighth cranial nerve of the cat. Intern J Neurosci 3:221-236, 1972
12. Goldberg JM, Fernandez C: Physiology of peripheral neurons innervating semicircular canals of the squirrel monkey. I. Resting discharge and response to constant angular accelerations. J Neurophysiol 34:635-660, 1971 13. Coldberg JM, Fernandez C: Physiology of peripheral neurons innervating semicircular
REPIUNTS - Richard R. Gacek, MD, Department of Otolaryngology, Upstate Medical Center, Syracuse, NY 13210.
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CALL FOR PAPERS OTO-RHINO-LARYNGOLOGICAL RESEARCH SOCIETY The next two meetings of the O.R.S. will be held as follows: April 11, 1980 at the University of Bristol: October 3, 1980 at the Royal National Throat, Nose and Ear Hospital, Gray's Inn Road, London. Those wishing to read a paper should submit an abstract (10 copies with the name and address on the top copy only) of not more than 250 words to the following: Professor P. Stell, ChM, FRCS, Secretary, Dept. of Otolaryngology, Royal Liverpool Hospital, Prescot Street, Liverpool. L7 8XP.
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