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Frequency Modulation of Afferent and Efferent Unit Activity in the Vestibular Nerve by Oculomotor Impulses
449
Frequency Modulation of Afferent and Efferent Unit Activity in the Vestibular Nerve by Oculomotor Impulses J. DICHGANS, C. L. S C H M I D T
AND
E. R. W I S T
Department of Neurology and Section of Neurophysiology, University of Freiburg, Freiburg i . Br., C .F.R.
Llinhs and Precht (1972) summarized the control of vestibular receptors by efferent fibres activated by stimulation of' the contralateral vestibular organ (Ledoux, 1958; Schmidt, 1963; Bertrand and Veenhof, 1964; Sala, 1965). They also described an ipsilateral efferent feedback passing through the vestibular parts of the cerebellum (Llinhs et al., 1967; Llinhs and Precht, 1969). Furthermore they cited numerous multisensory convergences upon efferent fibres in the vestibular nerve. For example efferent discharge-modulations can be elicited by active and passive movements of the extremities (Schmidt, 1963; Bertrand and Veenhof, 1964). They can also be elicited by stimulation of the skin, mainly in the head region, and by optokinetic stimuli (Klinke and Schmidt, 1970). The functional significance of these latter findings is not yet completely understood. It will be demonstrated here that saccadic eye movements (spontaneous saccades and the rapid phases of optokinetic and vestibular nystagmus) are associated with phasic discharge-modulations in the vestibular nerve. Most of the modulated neurones are efferent but some are certainly primary afferent fibres. These findings support the assumption that optomotor vestibular integration in animals already takes place at the receptor level. Single unit activity was recorded with tungsten microelectrodes from the left peripheral vestibular nerve of the goldfish (Carassius aureatus) and the rabbit (Lepus cuniculus). Eye movements were recorded simultaneously by means of photocells. The animals were neither relaxed nor anaesthetized, for it is known that narcotics inhibit the activity of efferent neurones (Schmidt, 1963). The experiments were carried out in enckphale isolk preparations. In order to investigate the neuronal response to adequate vestibular stimuli, the animals were placed on a Tonnies turn-table, and the microelectrode was inserted into the vestibular nerve under visual control with the aid of a microscope. In the goldfish preparation two electrode positions were selected: ( i ) in the fibres emerging from the horizontal canal; ( i i ) at the point right after the junction o t all afferent components of the vestibular nerve. For selective recording of efferent neurones the vestibular nerve was severed and activity was recorded from the proximal stump of the nerve detached from its receptors. The surgical procedures have been described in detail by Schmidt et al. (1970, 1972). References pp. 455-456
450
J. D I C H G A N S , C. I,. SCHMIDT, E. R . W I S T
In the rabbit the occipital bone was removed. The neuronal activity was recorded from the vestibular nerve in the posterior fossa at its entrance into the internal acoustic meatus (3 mm lateral of the brain stem surface). In some rabbits the ipsilateral cerebellum was ablated by suction. Since the findings in goldfish and rabbit were almost identical they will be described together. Species differences, where they occurred, will be separately described. Almost 10% of the neurones in the peripheral vestibular nerve show modulations of spontaneous activity in correlation with saccadic eye movements. Modulations occur regularly with all rapid eye movements, single saccades as well as the quick phases of optokinetic or vestibular nystagmus. Types of responses during saccadic eye movements
Four types of neurones could be differentiated. (ij Bidirectionally activated neurones (type-a), These are activated shortly before and during spontaneous saccades in both horizontal directions. Often the activation lasts longer than the duration of the saccade. In the goldfish most of the type-a neurones exhibit no or only low spontaneous activity (69 % 0-5 imp./sec), while in the rabbit the spontaneous activity averages 35 imp./sec. The activation starts 9-76 msec (mean: 33 msec) before the rapid eye movement. While the activation in the goldfish
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Fig. 1. Type-a neurone (rabbit). a, b: These records show clearly a gradual increase in spike frequency which occurs well before the onset of the saccade. The top line in each record indicates optokinetic nystagmus and the lower represents individual spikes from a single vestibular nerve fibre. c: the record shows that in the same neurone frequency modulation continues after administration of gallamine (lower line) even though no eye movements occur due to paralysis (upper line). On the right: graph showing the relationship between spike frequency (ordinate) and time before and after onset of a saccade (abscissa) averaged over 10 saccades in the same neurone as a-c.
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always reaches its peak frequency immediately, the discharge frequency in the rabbit can start up to 110 msec before the saccade with a slow rise and fall (Fig. I). (ii) Bidirectionally inhibited neurones (type-i). These are in most cases completely inhibited during saccades in both horizontal directions. The inhibition starts 18-96 msec (mean: 64 msec) before the onset of the saccade and quite clearly outlasts it. The inhibition has a mean duration of 250 msec (Fig. 2). Type-a neurones were found more frequently than type-i neurones. In the rabbit only the two types mentioned (a, i) were found." In the goldfish the existence of additional neurone-types (d, p) was established. (iii) Direction-specijic neurones (type-d). These are rare and are inhibited in correlation with saccaces to the ipsilateral side and activated with saccades to the contralateral side (Fig. 3). Here too frequency-modulation starts before the beginning of the saccade. (ii?) Eye position dependent neurones (type-p). Twenty-one percent of the eye movement correlated neurones of the goldfish showed clear tonic frequency-modulations depending upon eye position. A temporal deviation of the eye, ipsilateral to the microelectrode, causes an activation and a nasal deviation an inhibition. Only in this type of neurone did the alteration in frequency start up to 100 msec after the change in
* The interval between the onset of inhibition and saccade onset in type-i neurones and onset of activation and saccade onset in type-a neurones are not directly comparable due to a measurement artifact associated with the former. The measured interval is about 19 msec greater than its actual duration (Schmidt el al., 1972). References pp. 45s-456
452
J. D I C H G A N S , C . L. S C H M I D T , E. R. W I S T
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Fig. 3 . Type-d neurone (goldfish). Upper record: periodic alternating nystagmus (top line) which is also typically found in intact fish. Activation of vestibular neuronal activity during rapid phases to the right and inhibition to the left (bottom line). Lower graphs: averaged neuronal activity during 10 beats of nystagmus as in Fig. 2. Arrows indicate onset of rapid phase.
eye position. Consequently an initiation of frequency-modulation by proprioceptive afference from the eye muscles seems to be possible. Some of the type-p neurones showed an additional phasic type-a frequency-modulation in correlation with saccadic eye movements (Schmidt et al., 1972). In type-a, i and d neurones no consistent correlation could be found between the amplitude of eye movements and the degree of frequency-modulation. No relation to the slow phase of nystagmus could be traced. Neither the “crescendo neurones” nor the “decrescendo neurones” described by Duensing and Schaefer (1958) in the vestibular nuclei could be found in the vestibular nerve. Neurones of the macula-organs which can be stimulated by vibratory or acoustic stimuli showed no correlation with eye movements.
Functional considerations These findings may increase our knowledge about the coordination of eye movements and vestibular afferences. Even though this occurs mainly in the premotorial network of small reticular interneurones of the midbrain- and pontine tegmentum (Kornhuber, 1966), it also occurs in the vestibular nuclei and - as we could demonstrate - at the
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peripheral vestibular receptor level. Not only vestibular nystagmus but also spontaneous eye movements and optokinetic nystagmus are seen simultaneously with phasic frequency-modulations of neurones in the reticular formation and the vestibular nuclei. Eye movement-correlated neuronal discharges are found in the rabbit’s reticular formation near the mid-line of the tegmental rhombencephalon (Duensing and Schaefer, 1957) and in the vestibular nuclei (Eckel, 1954; Duensing and Schaefer, 1958). Similar phenomena in the peripheral vestibular nerve had not until now been discovered. The eye movement-correlated frequency-modulation of the neuronal types-a, i and d cannot be initiated by proprioceptive afference from the eye muscles, because it starts before the beginning of the saccade and can also be demonstrated after administration of gallamine which produces eye muscle paralysis (Fig. 1). OnIy the activity of type-p neurones, dependent upon eye position, may be modulated by proprioceptive reafference from the eye muscles. One of our experiments in which the eye was passively moved demonstrated that there exists a relationship between proprioceptive afference and frequency modulation of discharge frequency in the vestibular nerve. This result confirmed the findings obtained earlier by Schmidt (1963). It seems quite probable that the frequency-modulation in type-a, i and d neurones, which starts presaccadically is initiated by collaterals of the supranuclear optomotor centers. It wight be interpreted as a kind of supranuclear efference-copy (v. Holst and Mittelstaedt, 1950) or as corollary discharge (Teuber, 1960). It is unknown where the efferent fibres originate which conduct the information about saccadic eye movements to the peripheral vestibular organ. Among the efferent pathways known the most probabte is a fibre-bundle described by Rossi and Cortesina (1965). It originates homolaterally in the region of the pontine supranuclear oculomotor centers but also caudally in the dorsal reticular formation near the midline and goes to the vestibular nerve. At least in the rabbit the cerebellum has no influence upon the eye movement-correlated discharge-modulation in the peripheral vestibular nerve. Ablation of the ipsilateral cerebellum has no effect on the results described. Corresponding investigations in the goldfish were not performed. The question arises whether some of the neuronal types described can be identified as efferent and others as afferent neurones. Recordings from the proximal stump of the severed vestibular nerve in the goldfish yielded neurones of types-a, i and p. These were therefore identified as efferent neurones. Only the very rare direction-specific neurones (type-d) were not found in the proximal stump. Other neurones (a, i, p) of the intact vestibular nerve were identified as efferent neurones by their reaction to rotatory acceleration. They were activated by ampullofugal acceleration or by acceleration in both horizontal directions (types I1 and 111, described by Duensing and Schaefer, 1958). Such acceleration reactions characterize efferent neurones (Precht et al., 1971). In the goldfish it was not possible to verify that there existed afferent neurones with a frequency-modulation correlated with saccadic eye movements. Further experiments are in progress in which d.c.-recordings are made directly from the receptor layer. Such experiments could make clear the nature of the efferent influence. In the rabbit some type-a neurones could be identified as being afferent neurones on References pp. 455456
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the basis of their regular spontaneous activity (20-40 imp./sec), and their activation by ampullopetal acceleration. Small doses of barbiturate (2 mg/kg) extinguished the nystagmus-correlated activation, while the spontaneous activity and the response to acceleration were not influenced. The eye movements were abolished with higher dosages of'barbiturate (4 mg/kg). Since it is known that efferent fibres are inhibited by narcotics, one can presume that under barbituate influence information about saccades mediated by efferent fibres to the vestibular receptor cells is suppressed. Duensing and Schaefer (1958) drew attention to the narcotic sensitivity of eye movement correlated neurones in the vestibular nucleus also. The similarity of our results to those of Duensing and Schaefer (1957, 1958) raises the question of whether we recorded from secondary neurones of the nucleus interstitialis vestibularis. Some cells of this nucleus have been found in the most proximal part of the nerve in mammals (Gacek, 1969). In the goldfish similar cells in the peripheral nerve could not be verified histologically. It is quite obvious, however, that the vestibular neurones recorded directly from the ramus ampullaris lateralis in the dogfish were not secondary neurones. Definite statements about the functional significance of efierent eye movementcorrelated frequency-modulation in the peripheral vestibular nerve and the special task of each of the different typesofneuronescannot be madeat this time. It is striking that the phasic modulation is always linked with saccadic eye movements but cannot be found in pursuir movements and sloiv nystagmic phases. Mainly in the fish and frog, but also in the rabbit, saccadic eye movements are often supplemented by rapid head movements and optokinetic nystagmus by head-nystagmus. Control of vestibular afference during these head movements seems to be reasonable. During passive headmovements the elicited vestibular afference with its direct connection to oculomotor nuclei facilitates the steady fixation of a stationary visual target by inducing eye movements in a direction opposite to that of the head movement. During active head movement with eye movements in the same direction, the reverse afferent vestibular input to the oculomotor nuclei may be counterbalanced by efferent oculomotor impulses as far peripheral as at the vestibular receptor level. The efferent saccadic discharge-modulation in the vestibular nerve could thus serve as a compensation to the arriving afferent vestibular information during simultaneous head nystagmus in such a way, that the optokinetic nystagmus is not inhibited by opposite impulses for compensatory movements. The same can be assumed for the vestibular nystagmus which under physiological conditions supports the optokinetic nystagmus. Comparable results from the lateral line-organ were reported by Schmidt (1965). In the mud-puppy about 50 msec before active gill movements efferent discharges are elicited which reach the receptors of the lateral line-organ and might compensate for stimuli produced by the water streaming out of the gill. Contrary to eye movements, gill movements are purely vegetative reflex motions. Duensing and Schaefer (1960) established a descending modulation of reticular neurones linked to motor-efference during active head movements in the rabbit. During passive head movements these neurones were influenced by converging vestibular afferents in the opposite way. The
SACCADIC DISCHARGES IN VESTIBULAR N E R V E
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findings cited from the literature support the assumption of compensatory signals mediated by collaterals of the motor centers to the afferent sensory input acting not only in the higher integrating centers of the brain, but also on a more peripheral level. SUMMARY
1. Single unit activity was recorded from the peripheral vestibular nerve of unrelaxed and unanaesthetized goldfish and rabbits. Eye movements were registered. 2. Nearly 10 % of the neurones showed a frequency-modulation starting before the beginning of each spontaneous saccadic eye movement and rapid phase of optokinetic and vestibular nystagmus. 3. Bidirectionally activated (type-a) as well as bidirectionally inhibited (type-i) neurones could be established. In the goldfish a few direction-specific neurones with inhibition or activation depending upon the direction of horizontal saccadic eyemovements (type-d) were found. 4.The presaccadic initiated phasic discharge-modulation is supposed to originate from supranuclear optomotor centers. 5. In addition to these phasically modulated neurones found in both the goldfish and rabbit, the goldfish shows neurones whose discharge-frequency depends upon eye position (type-p). These neurones may be influenced by proprioceptive afferents from the eye muscle. 6 . Mainly in the goldfish, most of the neurones were identified as being efferent ones. In the rabbit some afferent bidirectionally activated neurones of type-a were verified. 7. The results demonstrate the existence of a vestibular control by oculomotor impulses mediated by efferent fibres to the vestibular receptor level in teleosts and lower mammals. The possible functional significance is discussed.
REFERENCES BERTRAND, R. A. AND VEENHOP, V. B. (1964) Efferent vestibular potentials by canalicular and otolithic stimulations in the rabbit. Acru oto-luryng. (Stockh.),58, 515-524. DUENSING, F. UND SCHAEFER, K. P. (1957) Die Neuronenaktivitat in der Formatio reticularis des Rhombencephalons beim vestibularen Nystagmus. Arch. Psychiut. Nervenkr., 196,265-290. DUENSING, F. UND SCHAEFER, K. P. (1958) Die Aktivitat einzelner Neurone im Bereich der Vestibulariskerne unter besonderer Berucksichtigung des vestibularen Nystagmus. Arch. Psychiut. Nervenkr., 198, 224252. DUENSING, F. UND SCHAEFER, K. P. (1960) Die Aktivitat einzelner Neurone der Formatio reticularis des nicht gefesselten Kaninchens bei Kopfwendungen und vestibularen Reizen. Arch. Psychiat. Nervenkr., 201, 97-122. ECKEL,W. (1954) Elektrophysiologische und histologische Untersuchungen irn Vestibulariskerngebiet bei Drehreizen. Arch. 0hr.- Nus.- u. Keh1k.-Heilk., 164, 487-513. GACEK,R. R. (1969) The course and central termination of first order neurones supplying vestibular endorgans in the cat. Actu oto-luryng. (Stoekh.), Suppl. 254, 1-66. HOLST,E. v. UND MITTELSTAEDT, H. (1950) Das Reafferenzprinzip (Wechselwirkung zwischen Zentralnervensystem und Peripherie). Naturwissenschaften, 37, 464476. KLINKE,R. AND SCHMIDT, C. L. (1970) Efferent influence on the vestibular organ during active movements of the body. PJriigers Arch. ges. Physiol., 318, 325-332.
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KORNHUBER, H. H. (1966) Physiologie und Klinik des vestibularen Systems. In J. BERENDES, R. ZINK AND F. ZOLLNCR (Eds.), Hals-Nasen-Ohrenheilkunde,ein kurzgeffisstes Handbuch. Vol. lIi13, Thieme, Stuttgart, pp. 2150-2351. LEDOUX, A., (1958) Les canaux semi-circulaires. Arta oto-rhino-luryng. belg., 12, 109-348. LLINAS,R . , PRECHT, W. A N D KITAI,S. T. (1967) Climbing fibre activation of Purkinje cell following primary vestibular afferent stimulation in the frog. Brain Res., 6, 371-375. LLINAS,R. AND PRECHT, W. (1969) The inhibitory vestibular efferent system and its relation to the cerebellum in the frog. Exp. Brain Res., 9, 1629. LLINAS,R. AND PRECHT,W. (1972) Vestibulocerebellar input: physiology. In A. BRODAL AND 0. POMPEIANO (Eds.), Progress in Brain Research. Vol. 37. Basic aspects of central vestibular mechanisrn5. Elsevier, Amsterdam, pp. 341-359. ROSSI,G. AND CORTESINA, G. (1965) The efferent cochlear and vestibular system in Lepus cuniculus. Acta anat. (Basel), 60, 362-381. PRECHT, W., LLINAS,R. A N D CLARKE, M. (1972) Physiological responses of frog vestibular fibers to horizontal angular rotation. Exp. Brain Res., 13, 378-407. SALA,0.(1965) The efferent vestibular system. Electro-physiological research. Acta oto-laryng. (Stockh.),SUPPI.197,4-34. SCHMIDT, C. L., WIST,E. R., DICHGANS, J. (1970) Alternating spontaneous nystagmus, optokinetic and vestibular nystagmus and their relationship to rhythmically modulated spontaneous activity in the vestibular nerve of the goldfish. Pfligers Arch. ges. Physiol., 319, R155-156. SCHMIDT, C. L., WIST,E. R. AND DICHGANS, J. (1972) Efferent frequency modulation in the vestibular nerve of goldfish correlated with saccadic eye movements. Exp. Brain Aes., 15, 1-14. SCHMIDT, R . S. (1963) Frog labyrinthine efferent impulses. Acta oto-luryng. (Stockh.), 56, 51-64. SCHMIDT, R . S. (1965) Amphibian acoustico-lateralis efferents. J . cell. romp. Physiol., 65,155-162. TEUBER, H. L. (1960) Perception. In J. FIELD,H. W. MAGOUN AND V. E. HALL(Eds.), Handbook of’ Physzology. Section 1 . Neurophysiolozy. Vol. Ill. Amer. Physiol. SOC., Washington, D.C., pp. 1595-1668.
Frequency Modulation of Afferent and Efferent Unit Activity in the Vestibular Nerve by Oculomotor Impulses J. DICHGANS, C. L. S C H M I D T
AND
E. R. W I S T
Department of Neurology and Section of Neurophysiology, University of Freiburg, Freiburg i . Br., C .F.R.
Llinhs and Precht (1972) summarized the control of vestibular receptors by efferent fibres activated by stimulation of' the contralateral vestibular organ (Ledoux, 1958; Schmidt, 1963; Bertrand and Veenhof, 1964; Sala, 1965). They also described an ipsilateral efferent feedback passing through the vestibular parts of the cerebellum (Llinhs et al., 1967; Llinhs and Precht, 1969). Furthermore they cited numerous multisensory convergences upon efferent fibres in the vestibular nerve. For example efferent discharge-modulations can be elicited by active and passive movements of the extremities (Schmidt, 1963; Bertrand and Veenhof, 1964). They can also be elicited by stimulation of the skin, mainly in the head region, and by optokinetic stimuli (Klinke and Schmidt, 1970). The functional significance of these latter findings is not yet completely understood. It will be demonstrated here that saccadic eye movements (spontaneous saccades and the rapid phases of optokinetic and vestibular nystagmus) are associated with phasic discharge-modulations in the vestibular nerve. Most of the modulated neurones are efferent but some are certainly primary afferent fibres. These findings support the assumption that optomotor vestibular integration in animals already takes place at the receptor level. Single unit activity was recorded with tungsten microelectrodes from the left peripheral vestibular nerve of the goldfish (Carassius aureatus) and the rabbit (Lepus cuniculus). Eye movements were recorded simultaneously by means of photocells. The animals were neither relaxed nor anaesthetized, for it is known that narcotics inhibit the activity of efferent neurones (Schmidt, 1963). The experiments were carried out in enckphale isolk preparations. In order to investigate the neuronal response to adequate vestibular stimuli, the animals were placed on a Tonnies turn-table, and the microelectrode was inserted into the vestibular nerve under visual control with the aid of a microscope. In the goldfish preparation two electrode positions were selected: ( i ) in the fibres emerging from the horizontal canal; ( i i ) at the point right after the junction o t all afferent components of the vestibular nerve. For selective recording of efferent neurones the vestibular nerve was severed and activity was recorded from the proximal stump of the nerve detached from its receptors. The surgical procedures have been described in detail by Schmidt et al. (1970, 1972). References pp. 455-456
450
J. D I C H G A N S , C. I,. SCHMIDT, E. R . W I S T
In the rabbit the occipital bone was removed. The neuronal activity was recorded from the vestibular nerve in the posterior fossa at its entrance into the internal acoustic meatus (3 mm lateral of the brain stem surface). In some rabbits the ipsilateral cerebellum was ablated by suction. Since the findings in goldfish and rabbit were almost identical they will be described together. Species differences, where they occurred, will be separately described. Almost 10% of the neurones in the peripheral vestibular nerve show modulations of spontaneous activity in correlation with saccadic eye movements. Modulations occur regularly with all rapid eye movements, single saccades as well as the quick phases of optokinetic or vestibular nystagmus. Types of responses during saccadic eye movements
Four types of neurones could be differentiated. (ij Bidirectionally activated neurones (type-a), These are activated shortly before and during spontaneous saccades in both horizontal directions. Often the activation lasts longer than the duration of the saccade. In the goldfish most of the type-a neurones exhibit no or only low spontaneous activity (69 % 0-5 imp./sec), while in the rabbit the spontaneous activity averages 35 imp./sec. The activation starts 9-76 msec (mean: 33 msec) before the rapid eye movement. While the activation in the goldfish
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ONSET OF R A P i D PHASF
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Fig. 1. Type-a neurone (rabbit). a, b: These records show clearly a gradual increase in spike frequency which occurs well before the onset of the saccade. The top line in each record indicates optokinetic nystagmus and the lower represents individual spikes from a single vestibular nerve fibre. c: the record shows that in the same neurone frequency modulation continues after administration of gallamine (lower line) even though no eye movements occur due to paralysis (upper line). On the right: graph showing the relationship between spike frequency (ordinate) and time before and after onset of a saccade (abscissa) averaged over 10 saccades in the same neurone as a-c.
451
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always reaches its peak frequency immediately, the discharge frequency in the rabbit can start up to 110 msec before the saccade with a slow rise and fall (Fig. I). (ii) Bidirectionally inhibited neurones (type-i). These are in most cases completely inhibited during saccades in both horizontal directions. The inhibition starts 18-96 msec (mean: 64 msec) before the onset of the saccade and quite clearly outlasts it. The inhibition has a mean duration of 250 msec (Fig. 2). Type-a neurones were found more frequently than type-i neurones. In the rabbit only the two types mentioned (a, i) were found." In the goldfish the existence of additional neurone-types (d, p) was established. (iii) Direction-specijic neurones (type-d). These are rare and are inhibited in correlation with saccaces to the ipsilateral side and activated with saccades to the contralateral side (Fig. 3). Here too frequency-modulation starts before the beginning of the saccade. (ii?) Eye position dependent neurones (type-p). Twenty-one percent of the eye movement correlated neurones of the goldfish showed clear tonic frequency-modulations depending upon eye position. A temporal deviation of the eye, ipsilateral to the microelectrode, causes an activation and a nasal deviation an inhibition. Only in this type of neurone did the alteration in frequency start up to 100 msec after the change in
* The interval between the onset of inhibition and saccade onset in type-i neurones and onset of activation and saccade onset in type-a neurones are not directly comparable due to a measurement artifact associated with the former. The measured interval is about 19 msec greater than its actual duration (Schmidt el al., 1972). References pp. 45s-456
452
J. D I C H G A N S , C . L. S C H M I D T , E. R. W I S T
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Fig. 3 . Type-d neurone (goldfish). Upper record: periodic alternating nystagmus (top line) which is also typically found in intact fish. Activation of vestibular neuronal activity during rapid phases to the right and inhibition to the left (bottom line). Lower graphs: averaged neuronal activity during 10 beats of nystagmus as in Fig. 2. Arrows indicate onset of rapid phase.
eye position. Consequently an initiation of frequency-modulation by proprioceptive afference from the eye muscles seems to be possible. Some of the type-p neurones showed an additional phasic type-a frequency-modulation in correlation with saccadic eye movements (Schmidt et al., 1972). In type-a, i and d neurones no consistent correlation could be found between the amplitude of eye movements and the degree of frequency-modulation. No relation to the slow phase of nystagmus could be traced. Neither the “crescendo neurones” nor the “decrescendo neurones” described by Duensing and Schaefer (1958) in the vestibular nuclei could be found in the vestibular nerve. Neurones of the macula-organs which can be stimulated by vibratory or acoustic stimuli showed no correlation with eye movements.
Functional considerations These findings may increase our knowledge about the coordination of eye movements and vestibular afferences. Even though this occurs mainly in the premotorial network of small reticular interneurones of the midbrain- and pontine tegmentum (Kornhuber, 1966), it also occurs in the vestibular nuclei and - as we could demonstrate - at the
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peripheral vestibular receptor level. Not only vestibular nystagmus but also spontaneous eye movements and optokinetic nystagmus are seen simultaneously with phasic frequency-modulations of neurones in the reticular formation and the vestibular nuclei. Eye movement-correlated neuronal discharges are found in the rabbit’s reticular formation near the mid-line of the tegmental rhombencephalon (Duensing and Schaefer, 1957) and in the vestibular nuclei (Eckel, 1954; Duensing and Schaefer, 1958). Similar phenomena in the peripheral vestibular nerve had not until now been discovered. The eye movement-correlated frequency-modulation of the neuronal types-a, i and d cannot be initiated by proprioceptive afference from the eye muscles, because it starts before the beginning of the saccade and can also be demonstrated after administration of gallamine which produces eye muscle paralysis (Fig. 1). OnIy the activity of type-p neurones, dependent upon eye position, may be modulated by proprioceptive reafference from the eye muscles. One of our experiments in which the eye was passively moved demonstrated that there exists a relationship between proprioceptive afference and frequency modulation of discharge frequency in the vestibular nerve. This result confirmed the findings obtained earlier by Schmidt (1963). It seems quite probable that the frequency-modulation in type-a, i and d neurones, which starts presaccadically is initiated by collaterals of the supranuclear optomotor centers. It wight be interpreted as a kind of supranuclear efference-copy (v. Holst and Mittelstaedt, 1950) or as corollary discharge (Teuber, 1960). It is unknown where the efferent fibres originate which conduct the information about saccadic eye movements to the peripheral vestibular organ. Among the efferent pathways known the most probabte is a fibre-bundle described by Rossi and Cortesina (1965). It originates homolaterally in the region of the pontine supranuclear oculomotor centers but also caudally in the dorsal reticular formation near the midline and goes to the vestibular nerve. At least in the rabbit the cerebellum has no influence upon the eye movement-correlated discharge-modulation in the peripheral vestibular nerve. Ablation of the ipsilateral cerebellum has no effect on the results described. Corresponding investigations in the goldfish were not performed. The question arises whether some of the neuronal types described can be identified as efferent and others as afferent neurones. Recordings from the proximal stump of the severed vestibular nerve in the goldfish yielded neurones of types-a, i and p. These were therefore identified as efferent neurones. Only the very rare direction-specific neurones (type-d) were not found in the proximal stump. Other neurones (a, i, p) of the intact vestibular nerve were identified as efferent neurones by their reaction to rotatory acceleration. They were activated by ampullofugal acceleration or by acceleration in both horizontal directions (types I1 and 111, described by Duensing and Schaefer, 1958). Such acceleration reactions characterize efferent neurones (Precht et al., 1971). In the goldfish it was not possible to verify that there existed afferent neurones with a frequency-modulation correlated with saccadic eye movements. Further experiments are in progress in which d.c.-recordings are made directly from the receptor layer. Such experiments could make clear the nature of the efferent influence. In the rabbit some type-a neurones could be identified as being afferent neurones on References pp. 455456
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the basis of their regular spontaneous activity (20-40 imp./sec), and their activation by ampullopetal acceleration. Small doses of barbiturate (2 mg/kg) extinguished the nystagmus-correlated activation, while the spontaneous activity and the response to acceleration were not influenced. The eye movements were abolished with higher dosages of'barbiturate (4 mg/kg). Since it is known that efferent fibres are inhibited by narcotics, one can presume that under barbituate influence information about saccades mediated by efferent fibres to the vestibular receptor cells is suppressed. Duensing and Schaefer (1958) drew attention to the narcotic sensitivity of eye movement correlated neurones in the vestibular nucleus also. The similarity of our results to those of Duensing and Schaefer (1957, 1958) raises the question of whether we recorded from secondary neurones of the nucleus interstitialis vestibularis. Some cells of this nucleus have been found in the most proximal part of the nerve in mammals (Gacek, 1969). In the goldfish similar cells in the peripheral nerve could not be verified histologically. It is quite obvious, however, that the vestibular neurones recorded directly from the ramus ampullaris lateralis in the dogfish were not secondary neurones. Definite statements about the functional significance of efierent eye movementcorrelated frequency-modulation in the peripheral vestibular nerve and the special task of each of the different typesofneuronescannot be madeat this time. It is striking that the phasic modulation is always linked with saccadic eye movements but cannot be found in pursuir movements and sloiv nystagmic phases. Mainly in the fish and frog, but also in the rabbit, saccadic eye movements are often supplemented by rapid head movements and optokinetic nystagmus by head-nystagmus. Control of vestibular afference during these head movements seems to be reasonable. During passive headmovements the elicited vestibular afference with its direct connection to oculomotor nuclei facilitates the steady fixation of a stationary visual target by inducing eye movements in a direction opposite to that of the head movement. During active head movement with eye movements in the same direction, the reverse afferent vestibular input to the oculomotor nuclei may be counterbalanced by efferent oculomotor impulses as far peripheral as at the vestibular receptor level. The efferent saccadic discharge-modulation in the vestibular nerve could thus serve as a compensation to the arriving afferent vestibular information during simultaneous head nystagmus in such a way, that the optokinetic nystagmus is not inhibited by opposite impulses for compensatory movements. The same can be assumed for the vestibular nystagmus which under physiological conditions supports the optokinetic nystagmus. Comparable results from the lateral line-organ were reported by Schmidt (1965). In the mud-puppy about 50 msec before active gill movements efferent discharges are elicited which reach the receptors of the lateral line-organ and might compensate for stimuli produced by the water streaming out of the gill. Contrary to eye movements, gill movements are purely vegetative reflex motions. Duensing and Schaefer (1960) established a descending modulation of reticular neurones linked to motor-efference during active head movements in the rabbit. During passive head movements these neurones were influenced by converging vestibular afferents in the opposite way. The
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findings cited from the literature support the assumption of compensatory signals mediated by collaterals of the motor centers to the afferent sensory input acting not only in the higher integrating centers of the brain, but also on a more peripheral level. SUMMARY
1. Single unit activity was recorded from the peripheral vestibular nerve of unrelaxed and unanaesthetized goldfish and rabbits. Eye movements were registered. 2. Nearly 10 % of the neurones showed a frequency-modulation starting before the beginning of each spontaneous saccadic eye movement and rapid phase of optokinetic and vestibular nystagmus. 3. Bidirectionally activated (type-a) as well as bidirectionally inhibited (type-i) neurones could be established. In the goldfish a few direction-specific neurones with inhibition or activation depending upon the direction of horizontal saccadic eyemovements (type-d) were found. 4.The presaccadic initiated phasic discharge-modulation is supposed to originate from supranuclear optomotor centers. 5. In addition to these phasically modulated neurones found in both the goldfish and rabbit, the goldfish shows neurones whose discharge-frequency depends upon eye position (type-p). These neurones may be influenced by proprioceptive afferents from the eye muscle. 6 . Mainly in the goldfish, most of the neurones were identified as being efferent ones. In the rabbit some afferent bidirectionally activated neurones of type-a were verified. 7. The results demonstrate the existence of a vestibular control by oculomotor impulses mediated by efferent fibres to the vestibular receptor level in teleosts and lower mammals. The possible functional significance is discussed.
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KORNHUBER, H. H. (1966) Physiologie und Klinik des vestibularen Systems. In J. BERENDES, R. ZINK AND F. ZOLLNCR (Eds.), Hals-Nasen-Ohrenheilkunde,ein kurzgeffisstes Handbuch. Vol. lIi13, Thieme, Stuttgart, pp. 2150-2351. LEDOUX, A., (1958) Les canaux semi-circulaires. Arta oto-rhino-luryng. belg., 12, 109-348. LLINAS,R . , PRECHT, W. A N D KITAI,S. T. (1967) Climbing fibre activation of Purkinje cell following primary vestibular afferent stimulation in the frog. Brain Res., 6, 371-375. LLINAS,R. AND PRECHT, W. (1969) The inhibitory vestibular efferent system and its relation to the cerebellum in the frog. Exp. Brain Res., 9, 1629. LLINAS,R. AND PRECHT,W. (1972) Vestibulocerebellar input: physiology. In A. BRODAL AND 0. POMPEIANO (Eds.), Progress in Brain Research. Vol. 37. Basic aspects of central vestibular mechanisrn5. Elsevier, Amsterdam, pp. 341-359. ROSSI,G. AND CORTESINA, G. (1965) The efferent cochlear and vestibular system in Lepus cuniculus. Acta anat. (Basel), 60, 362-381. PRECHT, W., LLINAS,R. A N D CLARKE, M. (1972) Physiological responses of frog vestibular fibers to horizontal angular rotation. Exp. Brain Res., 13, 378-407. SALA,0.(1965) The efferent vestibular system. Electro-physiological research. Acta oto-laryng. (Stockh.),SUPPI.197,4-34. SCHMIDT, C. L., WIST,E. R., DICHGANS, J. (1970) Alternating spontaneous nystagmus, optokinetic and vestibular nystagmus and their relationship to rhythmically modulated spontaneous activity in the vestibular nerve of the goldfish. Pfligers Arch. ges. Physiol., 319, R155-156. SCHMIDT, C. L., WIST,E. R. AND DICHGANS, J. (1972) Efferent frequency modulation in the vestibular nerve of goldfish correlated with saccadic eye movements. Exp. Brain Aes., 15, 1-14. SCHMIDT, R . S. (1963) Frog labyrinthine efferent impulses. Acta oto-luryng. (Stockh.), 56, 51-64. SCHMIDT, R . S. (1965) Amphibian acoustico-lateralis efferents. J . cell. romp. Physiol., 65,155-162. TEUBER, H. L. (1960) Perception. In J. FIELD,H. W. MAGOUN AND V. E. HALL(Eds.), Handbook of’ Physzology. Section 1 . Neurophysiolozy. Vol. Ill. Amer. Physiol. SOC., Washington, D.C., pp. 1595-1668.