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Multisensory Influence Upon Single Units in the Vestibular Nucleus JOHN M. FREDRICKSON AND DIETRICH SCHWARZ University of Toronto SUMMARY Cells in the vestibular nucleus responsive to vestibular end-organ and joint stimulation have been studied by the method of single-unit analysis in the unanesthetized cat. Ninety-nine percent of the units responded to vestibular stimulation and 80 percent to joint movement. There were no responses to muscle pressure, or to optic or acoustic stimuli. The convergent pattern of the two effective sensory systems on single cells was usually summative. Cerebellectomy did not grossly alter the pattern of joint influence. The vestibular cells responsive to joint movement function to detect the angular positions of joints, and through discharge patterns indicate the rate and direction of movement, as well as the steady position of joints. The convergence of the two main position-sense receptors (joints and labyrinth) in the vestibular nucleus is discussed from the standpoint of its significance for rapid, reflex, postural adjustments and postural stability. INTRODUCTION Head-position information is provided by the vestibular labyrinth: The otolith organs signal the axis of rotation relative to gravity, whereas the axis of rotation relative to the head is moni- tored by the semicircular canals. To make rapid, reflex, postural adjustments, however, the central nervous system must receive position information concerning the relative position of the head upon the body. Logically, neck-position afferents must play an important role in informing the central nervous system where the body is in space relative to the head. In fact, it is known that severe disturbances of body equilibrium occur following ablation of Cl, C2, and C3 dorsal roots in the cat (ref. 1) and monkeys (ref. 2). Other classic neurophysiological investigations (refs. 3 to 5) have demonstrated the need for integration of vestibular and deep somatosensory (proprioceptive) afferents in postural regulation; however, the question remained as to where this positional information converged in the central nervous system to bring about the necessarily rapid, reflex, postural adjustments. In this study, single units were sampled in the vestibular nucleus of cats in order to determine â (1) Whether convergence of deep somatosen- sory and vestibular input occurs, and if so, how frequently and in what way. (2) Whether acoustic or visual input has any influence. (3) Whether the pattern of responses is grossly altered following cerebellectomy. METHOD This single-unit study was carried out on 21 cats not under the influence of general anesthesia. These animals were immobilized during the experiment with gallamine triethiodide (Flaxedil). A long-acting local anesthetic was infiltrated into 203
204 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION incised and pressure-point areas. Two of these animals underwent cerebellectomy. (Further details as to methodology are available, ref. 6.) Stimuli consisted of diffuse white light directed onto open eyes (both continuous illumination and intermittent illumination with light phases and dark phases of equal duration were used), hand- claps and whistles, galvanic stimulation (0.05 to 0.12 mA) delivered through round-window mem- brane electrodes, and, finally, somatosensory stimulation which included blowing on the fur, gently touching the skin, deep muscle pressure, and joint movement. The location of all of the neurons sampled with steel microelectrodes was verified histologically. One hundred and thirty- seven neurons were thoroughly analyzed; approxi- mately 50 percent were located in the descending vestibular nucleus, 30 percent in the medial nucleus, and 20 percent in the lateral (Deiters') nucleus. RESULTS Some of the more pertinent details previously reported (ref. 6) for most of the units in this study will herein be summarized. New data, spe- cifically concerning single-unit responses to joint movement, will be presented. Optic and Acoustic Responses There were no such responses, but it must be stressed that the analysis was visual. Thus a very subtle neuronal response, particularly if it had a very long latency, may have been missed. Vestibular Responses Ninety-nine percent of the neurons analyzed responded to labyrinthine polarization with short latencies. Approximately 10 percent of the units responded exclusively to ipsilateral stimulation, whereas 4 percent responded to contralateral stimulation alone. The most rapid responses ipsilaterally were monosynaptic. accounting for approximately 50 percent of the neurons analyzed with latencies of 0.5 to 0.7 msec. Fifteen per- cent of the units responding to contralateral labyrinthine polarization had latency values which were below 1.5 msec. A few of these units were analyzed on fast film and were found to respond between 0.7 and 0.9 msec. Thus it would appear that there is a small population of neurons in the vestibular nucleus served mono- synaptically from the contralateral vestibular labyrinth. Neuronal responses were broken down into direction-dependent and direction-independent types. The first term implies that the response changed with a reversal of the polarizing currents, whereas the second term implies a fixed response regardless of the direction of the polarizing cur- rent. The most common response, that is, acti- vation with ipsilateral cathodic stimulation (fig. 1), is the same as that produced by stimulation of the lateral semicircular canal by ipsilateral rota- tional acceleration or hot calorization (refs. 7 to 9). This most common ipsilateral response occurred approximately 55 percent of the time. A more complete analysis of the responses to labyrinthine polarization has been reported (ref. 6). cathod. polar, contralat. Labyr. anod.polar, contralat. labyr. FIGURE 1. â Neuron located in the descending vestibular nucleus which responded mono- svnaptically to labvrinthine polarization. This particular response was preponderant and was termed "direction dependent" as there was a response reversal with a reversal of polarization.
MULTISENSORY INFLUENCE IN THE VESTIBULAR NUCLEUS 205 Somatic Responses Approximately 80 percent of the neurons ana- lyzed responded to joint movement (propriocep- tive or "deep" stimulation). Only three units responded to skin stimulation (exteroceptive or "superficial"). There were no responses to deep muscle pressure; this is in agreement with a previous study (ref. 10) demonstrating that there were no responsive Deiters' neurons upon elec- trically stimulating group la nerve fibers which arise exclusively from muscle spindles. Exteroceptive responses, rarely noted in the vestibular nucleus, have a wider effect upon neurons in the reticular formation (refs. 11 to 14). The exteroceptive system, which is known to play an important role in skilled aimed move- ments, does not, from this study, appear to have much direct influence on rapid, reflex, postural adjustments. The general distribution of responses from joints was 40 percent from the vertebral column alone, 40 percent from both vertebra and limbs, and 20 percent from the limbs alone. Approxi- mately 45 percent of the total number of joint- responsive units responded to neck movement. Ipsilateral joint responses exceeded contra- lateral responses by 2 to 1, and proximal joint responses exceeded peripheral responses by almost 5 to 1. This preponderance of proximal joint influence upon the neurons was significant. It has been previously shown (ref. 15) that proximal joint-position sense is more acute than distal, both with respect to distance and rate-of- movement stimulus. It appeared that all units affected by joint movement responded immediately, although exact latency times could not be measured. The great majority of the responses were excitatory in nature. A few neurons appeared to be in- hibited by reciprocal joint movement. This was especially true for units influenced by neck movement. A more detailed analysis of joint responses is contained in a previous communica- tion (ref. 6). The maximum rate of neuronal discharge appeared to correspond with the maximum joint displacement; however, an exact evaluation of the joint angle versus neuronal discharge was not carried out. Thus, a further nine vestibular units, responsive to joints, have been studied more closely. The joints were moved by hand, but care was taken to move only the joint in question, which was generally the only activating source. Joint angles were measured with a standard orthopedic device. None of these additional units were inhibited by the reciprocal joint movement which provoked activation. On this occasion, as well as noting that the neurons were activated maximally at an extreme range of joint movement, we also noted that successively smaller degress of joint move- ment produced successively lower frequencies of discharge (fig. 2). Thus from a threshold posi- tion, if flexion was the activating joint movement, the neuron discharged at more rapid frequencies as the joint moved toward the maximal angle of flexion (fig. 3). It can be seen from figure 3 that, at each angle of excitation, there is a steady 1 ; nnnrt nolnr incjlnt l/ihwr-. . FIGURE 2. â Unit located in the lateral vestibular nucleus responsive to both vestibular and joint stimulation. The inhibition produced by ipsilateral anodic labyrinthine polariza- tion is included in order that one may compare the "resting" activity following the vestib- ular stimulation with the discharge rate on the second line during extension of ipsilateral elbou: Unit activity at 130Â° of extension is less than that at 170Â°. Maximum joint extension resulted in the maximum discharge rate. Flexion did not influence the resting activity of the unit.
206 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION 120 80 -= 40 DEGREES OF ELBOW FLEXION r*" i" 100 20 60 Seconds FIGURE 3. âGraphic illustration of the excitatory response pattern of a neuron located in the medial vestibular nucleus. Increasing angles of elbow flexion produced increasing levels of neuronal activity. Note the initially marked transient increase in discharge as the joint is moved to a new angle, followed by a steady discharge level peculiar to that angle. state of discharge which appears to be specific to that angle. The angular range of joint move- ment producing activation was large, averaging approximately 100Â°. These characteristics have also been noted with joint-responsive neurons in the thalamus and cortex of the Rhesus monkey (refs. 16 and 17). Convergence and Interaction Approximately 80 percent of all the neurons responded to both labyrinthine and joint stimu- lation. Interaction was thoroughly investigated for approximately 40 units, and the results were almost invariably summative. On a few occa- sions a complex interaction was observed. Cerebelleetomy Preparations Fourteen neurons were studied in two cere- bellectomized animals. Eleven responded to both labyrinthine and joint stimulation, while three responded to labyrinthine stimulation alone. Thus, it appeared that the cerebellum did not, in any major way, alter the distribution of the effective stimuli. DISCUSSION Mechanism of Spinovestibular Influence There is a great deal of evidence to support the view that somatic influence has a direct effect upon some units in the vestibular nucleus: (1) Spinovestibular fibers have been found to ter- minate directly in certain portions of the vestib- ular nucleus (refs. 18 and 19); (2) we found that large doses of barbiturates did not eliminate the effect of joint movements; and (3) cerebel- lectomy did not abolish or grossly alter the somatic influence upon vestibular units. The possibility that some somatic impulses ascend via the reticular formation cannot be excluded; however, in a similarly constructed parallel study, Potthoff, Richter, and Burandt found far fewer neuronal responses to joint movement in the bulbar and pontine reticular formation (ref. 20). Other neurophysiological studies have also demonstrated very little in the way of joint responses in the reticular formation (refs. 11, 12, and 14). Significance of Vestibular and Joint Interaction These results, which have demonstrated an almost exclusive deep somatosensory influence upon vestibular neurons, correlates well with the known facts that reflex postural adjustment de- pends upon impulses from the vestibular laby- rinth and deep sensory receptors. It is interesting that deep muscle pressure did not influence the single units recorded. Flaxedil does not appear to abolish muscle responses (H. D. Hen- atsch, personal communication) and therefore cannot be implicated in explaining why muscle pressure was ineffective. Certainly joint movement has been shown to be exquisitely sensitive as a postural indicator. Magnus and Storm van Leeuwen (ref. 1) pro- duced a syndrome in cats somewhat resembling a bilateral labyrinthectomy by cutting the dorsal roots of Cl, C2, and C3, and Cohen (ref. 2) noted an even more marked labyrinthine-like deficit in monkeys following section or local anesthetization of Cl, C2, and C3 dorsal roots. McCouch, Deering, and Ling (ref. 21) demon- strated that the receptors for the tonic neck reflex appeared to be exclusively located within C1,C2, and C3 joints.
MULTISENSORY INFLUENCE IN THE VESTIBULAR NUCLEUS 207 It would appear from this study that proximal limb and neck joints play an especially promi- nent role in supplying postural information to the vestibular nuclei. At this brainstem station, the information can be dealt with immediately, permitting essential, rapid, reflex, postural adjust- ments. The receptor organs for joint movement im- pulses have been traced by dissection and appear to be located in the joint capsule and pericapsular connective tissue (ref. 16). The joint-position information noted in the vestibular nucleus must arrive via the spinovestibular tract (refs. 18 and 19). The discharge patterns and frequencies of the units studied in the vestibular nucleus responding to joint movement provided information concern- ing the direction, rate of movement, and the steady position of the limbs. Mountcastle, Poggio, and Werner (ref. 17) made similar obser- vations for single units in the ventrobasal nuclear complex of the Rhesus thalamus, and they have thoroughly discussed the possible significance. They also reviewed the variations in response patterns noted at stations other than the vestibu- lar nuclei receiving position-sense information from the joints; that is, the first-order afferents, the thalamus, and the sensory cortex. Position information from the joints and vestibular labyrinth appears to ascend together in the central nervous system. We have found (ref. 22) that the primary cortical vestibular re- ceiving area in the Rhesus corresponds to that portion of the somatosensory cortex where Mount- castle noted such prominent joint input. Pre- sumably, short-latency vestibular responses in the thalamus would also be located in the same areas as the joint input, that is, in the ventrobasal nuclear complex; however, this has not been proven. REFERENCES 1. MAGNUS. R.; AND STORM VAN LEEUWEN, W.: Die Akuten und die dauernden Folgen des Ausfalles der tonischen Hals und Labyrinthreflexe. Pliigers Arch, ges. Physiol., vol. 159, 1914, p. 157. 2. COHEN, L. A.: Role of Eye and Neck Proprioceptive Mechanisms in Body Orientation and Motor Coordina- tion. J. Neurophysiol., vol. 24,1961, pp. 1-11. 3. McNALLY, W. J.; AND TAIT, J.: Ablation Experiments on the Labyrinth of the Frog. Am. J. Physiol.. vol. 75, 1925. pp. 155-179. 4. MAGNUS, R.: Kiirperstellung. Monographien aus dem Gesamtgebiet der Physiologie der Pflanzen und der Tiere. Julius Springer (Berlin), 1924. 5. SHERRINGTON, C. S.: Decerebrate Rigidity and Reflex Co-ordination of Movements. J. Physiol., vol. 22,1898, p. 319. 6. FREDRICKSON, J. M.; SCHWARZ, D.; AND KORNHUBER, H. H.: Convergence and Interaction of Vestibular and Deep Somatic Afferents Upon Neurons in Vestibular Nuclei of the Cat. Acta Oto-Laryngol.. vol. 61, 1966. pp. 168-188. 7. DUENSING. F.: AND ScHAEFER. K.-P.: Die Aktivitat einzelner Neurone im Bereich der Vestibulariskerne bei Horisontalbeschleunigungen unter besonderer Beriicksichtigung des vestibularen Nystagmus. Arch. Psychiat., vol. 198. 1958. pp. 225-252. 8. ECKEL, W.: Elektrophysiolojasche und histologische Untersuchungen im Vestibulariskerngebiet bei Dreh- reizen. Arch. Ohr.-. Nas.-. u. KehlkHeilk. vol. 164, 1954. pp. 487-513. 9. GERNANDT, B. E.: Response of Mammalian Vestibular Neurons to Horizontal Rotation and Caloric Stimula- tion. J. Neurophysiol., vol. 12, 1949, pp. 173-184. 10. GlAQUINTO, S.; POMPEIANO, O.; AND SANTINI, M.: Risposte di Unita Deitersiane a Stimolazione Graduata di Nervi Cutanei e Muscolari in Animali Decerebrati a Cervelletto Integro. Boll. Soc. Ital. Biol. sper., vol. 39. 1963, pp. 524-527. 11. BACH-Y-RlTA, P.: Convergent and Long-Latency Unit Responses in the Reticular Formation of the Cat. Exptl. Neurol., vol. 9, 1964. pp. 327-344. 12. BELL, C.: SIERRA, G.; BUENDIA, N.: AND SEGUNDO, J. P.: Sensory Properties of Neurons in the Mesencephalic Reticular Formation. J. Neurophysiol., vol. 27, 1964, pp. 9 6 1-987. 13. POTTHOFF. P. C.: AND BURANDT, H. R.: Neuronale Antworten auf vestibulare Reize im Tectum und pontomesencephalen Tagmentum der Katze und ihre Konvergenz mit optischen, akustischen und somatosensiblen Afferenzen. Pfliigers Arch. Ges. Physiol., vol. 281, 1964, p. 130. 14. SCHEIBEL, M. E.; SCHEIBEL, A.; MOLLICA, A.: AND MORUZZI, G.: Convergence and Interaction of Afferent Impulses on Single Units of Reticular Formation. J. Neurophysiol., vol. 18, 1955, pp. 309-311. 15. GARDNER. E.: Physiology of Moveable Joints. Physiol. Rev., vol. 30, 1950. pp. 127-176. 16. MOUNTCASTLE, V. B.; AND POWELL. T. P. S.: Central Nervous Mechanisms Subserving Position Sense and Kinethesis. Bull. Johns Hopkins Hospital, vol. 105. 1959, pp. 173-200. 17. MOUNTCASTLE, V. B.; Poccio, G. F.; AND WERNER, G.:
208 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION The Relation of Thalamic Cell Response to Periph- eral Stimuli Varied Over an Intensive Continuum. J. Neurophysiol., vol. 26, 1963. pp. 807-834. 18. MEHLER, W. R.; FEFERMAN, M. E.; AND NAUTA, W. J. H.: Ascending Axon Degeneration Following Antero- lateral Chordotomy: An Experimental Study in the Monkey. Brain, vol. 83, 1960, pp. 718-750. 19. POMPEIANO, O.; AND BRODAL. A.: Spino-vestibular Fibers in the Cat: An Experimental Study. J. Comp. Neurol., vol. 108, 1957, pp. 353-382. 20. POTTHOFF. P. C.; RlCHTER. H. P.; AND BURANDT, H. R.: DISCUSSION Precht: I think it has become clear by now that the vestibular nuclei and the neurons in this nucleus are by no means simple relay cells that lead to some reflex action, but rather very complicated centers for integration of various inputs. Torok: I want to confirm a statement that Dr. Fredrickson made about whiplash injury and subsequent postural vertigo and nystagmus. We have seen recently several patients with a diagnosis of "whiplash injury." Dizziness was the com- plaint. The cochlear and vestibular sensitivity appeared to be normal and fully symmetrical. Upon postural stimu- lation, however, in certain head positions, short vertigo and nystagmus was repeatedly observed. Contrary to the more typical benign paroxysmal postural vertigo syn- drome, the elicited postural dizziness and nystagmus showed no fatigue at all. Precht: Did I understand you correctly that pressure on the muscle, even on the neck muscles, did not have any influence on the discharge frequency of vestibular neurons? Changes in frequency of firing did occur on passive head movements? Fredrickson: That is right. We actually had to move the joint. This surprised us a great deal initially: therefore, we took great pains to stabilize the joint which was actually producing the effect, and then to retest the effect of deep muscle pressure. It was very clear that deep muscle pressure did not seem to have any effect. We wondered whether the Flaxedil was playing some role in preventing muscle influence. Multisensorische Konvergenzen an Hirnstammneu- ronen der Katze. Arch. Psychiat. Nervenkr., vol.210. 1967, p. 36. 21. McCoucH. G. P.: DEERING, I. D.; AND LING. T. H.: Location of Receptors for Tonic Neck Reflexes. J. Neurophysiol., vol. 14, 1951, pp. 190-195. 22. FREDRICKSON, J. M.: FIGGE. U.; SCHEID. P.: AND KORN- HUBER. H. H.: Vestibular Nerve Projection to the Cerebral Cortex of the Rhesus Monkey. Exptl. Brain Res., vol. 2, 1966, pp. 318-327. but from the literature there is no evidence to suggest Flaxedil inhibits muscle spindle activity. Waite: How many degrees of deviation in the cervical joints do you think you stimulated with, approximately? Fredrickson: I would say approximately 60" was maximum. Waite: Would you care to comment on the effect of 1Â° or 2Â°, or perhaps less than 1Â° of deviation? Fredrickson: Yes; small degrees of deviation would also cause the effect. We did not closely study the effect of degrees of neck deviation versus neuronal activity. We did for a few of the limb joint neurons as it was much easier to more exactly ascertain the limb joint angle, but certainly small degrees of movement of the neck did cause activation. Lowenstein: Presumably the whole of the vestibular nerve was polarized? Fredrickson: Perhaps; however, the stimulating current was very small. In all likelihood we surely stimulated more than one portion of the vestibular end organ. Lowenstein: I think you had 30 percent conforming to the picture I described. You must not forget that 1 polarized through the recording electrode directly at the ampullary sense ending; therefore, I am not surprised at the percentage. I think you were rather lucky to get consistent results. Fredrickson: Yes; only 30 percent responded that way. There were several combinations of responses to polariza- tion, so our results were really quite mixed.