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Vestibular, somatosensory, and auditory input to the thalamus of the cat
EXPERIMENTAL
Vestibular,
NEUROLOGY
65, 343-354
Somatosensory, Thalamus P.
Department of Neurology, York, New York 10032,
S. BLUM
(1979)
and Auditory of the Cat AND
Input to the
S. GILMAN’
College of Physicians and Surgeons, Columbia University, New and Department of Physiology, Thomas Jefferson University, Philadelphia. Pennsylvania 19107
Received
March
5, 1979
Responses were recorded and analyzed for 334 single units in the ventral, posterior, and intralaminar groups of thalamic nuclei of the cat. Units were tested for a response after (i) electrical stimulation of the vestibular nerve; (ii) electrical stimulation of the four paw pads and natural stimulation of joint, muscle, and cutaneous receptors of the limbs, trunk, and head (somatic stimulation); and (iii) electrical stimulation of the cochlear nerve and sound (auditory stimuli). Forty-one percent of the units responded to these stimuli. Vestibular stimulation activated 16% of the responsive units. These units were found primarily in the posterior nucleus and the border region between it and the ventral posterolateral nucleus. Seventy-three percent of vestibular-activated units also responded to at least one other modality of sensory stimuli. No evidence was found for a thalamic region where the majority of units responded at short latency to vestibular nerve stimulation. Ninety percent of the responsive units were activated by somatic stimuli. These units could be divided into two groups. One group was composed of units that were activated exclusively by somatic stimuli and had a small contralateral receptive field. These units were found primarily in the ventral posterolateral nucleus. The other group had a bilateral receptive field or was activated by more than one modality of sensory stimuli. These units were. found primarily in the posterior nucleus and the border area of the ventral posterolateral nucleus. Units that responded to auditory stimulation (10% of responsive units) were found in the posterior nucleus and the medial geniculate nucleus. Abbreviations: VPL-ventral posterolateral nucleus, PO-posterior nucleus. 1 Partially supported by U.S. Public Health Service grant NSll307. The present address of Dr. Blum is Department of Physiology, Thomas Jefferson University and that of Dr. Oilman is Department of Neurology, University of Michigan, Ann Arbor, MI 48109.
343 0014-4886/79/080343-12$02.00/O Copyright 0 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
344
BLUM
AND
GILMAN
INTRODUCTION Several investigators have used evoked potential techniques to explore the thalamic projections of the ascending components of the vestibular system (1, 7, 9, 16, 20). In a recent study, Blum et al. (7) used these techniques to survey the thalamic nuclei that had been shown, in separate anatomical experiments, to contain neurons projecting to the vestibular receiving regions of the cerebral cortex. Short-latency (~3.5 ms) and high-amplitude evoked potentials were found in the ventral posterolateral nucleus (VPL) and the rostra1 part of the posterior nucleus (PO). It was concluded that neurons in VPL and the rostra1 part of PO constitute an important component of the thalamic nuclei that relay vestibular activity to the cerebral cortex at short latency. Although valuable, evoked potential studies have the shortcomings that their precise localizing value is limited and the responsiveness of individual neurons to vestibular and other modalities of stimulation cannot be determined. The issue of the responsiveness to various modalities of stimulation of vestibular-activated neurons in the thalamus is important because the auditory and somatosensory systems have a strong representation in the region of the thalamus showing vestibular-evoked potentials (2, 4, 18). Thus far, only two studies have been made of the responses of single thalamic neurons to vestibular nerve stimulation. In the squirrel monkey, Liedgren et al. (15) examined the responses to sensory stimuli of single neural units in the ventral, posterior, and intralaminar groups of nuclei. They found vestibular-activated neurons throughout the region investigated. More than 60% of vestibular-activated neurons also responded to somatosensory or auditory stimuli. Evoked potential studies of the ascending vestibular system projections in the monkey, however, showed that large-amplitude responses are in a region different from that in the cat (10). There is only one study of thalamic unit responses to vestibular and other stimuli in the cat. Blum et al. (6) recorded the responses of neurons in the posterior portion of the PO to auditory and somatosensory stimuli. They found that only 5% of the neurons were activated by vestibular nerve stimulation. These neurons showed long-latency responses to vestibular stimulation and multimodal responses, including vestibular, auditory, and somatosensory stimuli. These neurons were outside the region containing large-amplitude, short-latency vestibular evoked potentials. Consequently, these data represent only a partial characterization of the thalamic nuclei involved in the processing of ascending vestibular activity. The present studies were designed to use single-unit recordings for determining the responses of single thalamic neurons to vestibular and other modalities of stimulation. The data show that vestibular-activated
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TO THALAMUS
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neurons are situated in the PO and in the border between the PO and the VPL and that most of these neurons also respond to somatosensory and/or auditory stimulation. METHODS Adult cats weighing between 2.0 and 3.5 kg were anesthetized with alpha-chloralose (60 mg/kg, i.v.). Cannulas were placed in the trachea and in a femoral vein and artery. The blood pressure was maintained above 90 mm Hg with 6% dextran in saline, if necessary, and the body temperature was maintained at 37°C with a thermostatically controlled heating pad. The animals were paralyzed with gallamine triethiodide (Flaxedil) and respired artificially during recording. A bipolar electrode was placed on the right vestibular nerve, and a second electrode was placed on the right cochlear nerve. Stimulation was applied through the electrode on the vestibular nerve with a 0. 1-ms pulse. Stimulus intensity was adjusted during recordings of averaged potentials from electrodes in the lateral vestibular and dorsal cochlear nuclei. The intensity was set in each experiment so that fibers of the vestibular nerve were excited but fibers in the nearby cochlear nerve were not affected (low-intensity vestibular stimulation). The procedure to determine the value for low intensity vestibular stimulation was described previously (1, 6,7,9). The stimulus intensity of a O.l-ms pulse delivered to the cochlear nerve was adjusted in an analogous manner. In some experiments, the effect of low-intensity vestibular stimulation was monitored with a monopolar electrode on the vestibular projection area of the cerebral cortex. Recordings were obtained from the cerebral cortex to show that the ascending vestibular pathway was active during the experiments. Natural stimulation was used to assess unit responsiveness to stimulation of joint, muscle, and cutaneous receptors of the limbs and trunk (somatosensory stimuli). Flexion and extension of the joints of all four limbs and the vertebral column were used forjoint and muscle stimulation. Blowing and light brushing across the fur of the limbs, face, and trunk were used for cutaneous stimulation. Sound (clicks, hand claps) was used to stimulate the cochlear receptors. Electrical stimulation was applied to the paw pads through needle electrodes placed on either side of the central portion of the paw. Stimuli consisted of 0. I-ms square wave pulses at 10 V. The activity of single neural units was recorded in the thalamus with glass microelectrodes filled with either 2 M NaCl saturated with fast green dye or 2 M NaCl. Standard amplification and display techniques were used. Stimulation of the vestibular nerve at 0.3 Hz was used as a “hunting” stimulus as the recording electrode was advanced into the thalamus. To
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ensure that neural units responsive to vestibular stimulation would be found, the intensity of vestibular nerve stimulation was set at 5 to 10 times the low-intensity vestibular stimulation value (high-intensity vestibular stimulation). Units responsive to high-intensity vestibular stimulation and those showing activity without overt stimulation (spontaneous activity) were recorded and analyzed. Each unit was tested with a standard battery of stimuli, including (i) vestibular nerve electrical stimulation at 0.3 Hz, both high- and low-intensity; (ii) electrical stimulation of the cochlear nerve at 0.3 Hz; (iii) natural auditory stimulation; and (iv) somatic stimulation. Units were considered responsive to an electrical stimulus if a stimuluslocked response occurred in at least 50% of the 16 to 32 stimulus trials. The responsiveness of each unit to the natural stimuli was assessed by observing its activity with an oscilloscope and an audio monitor before, during, and after stimulation. On completion of each electrode penetration, a small fast green mark or electrolytic lesion was made at the bottom of the track by passing 5 to 20 PA current with the electrode negative for 5 to 10 min. The site of recording of each unit was determined by the stereotaxic parameters taken at the time of recording and subsequent histological examination of the tissue. RESULTS The activity of 334 units was recorded during 54 electrode penetrations through the thalamus. Forty-one percent (136) of the units responded to one or more of the stimuli. Units unresponsive to the stimuli were found throughout the thalamus, often adjacent to responsive units in a single electrode penetration (Fig. 1). Some units were responsive only to one modality of stimuli and are termed “unimodal.” Other units responded to more than one modality and are termed “multimodal.” Table 1 contains a summary of the different groups of units based upon their responses to vestibular, auditory, and somatic stimuli. Vestibular stimulation activated 16% (22) of the responsive units (Fig. 2). The responses of two units to vestibular stimulation are shown in Fig. 3. The latencies of the initial spike after vestibular stimulation for all vestibular-activated units were from 4 to 24 ms (Fig. 4C). Six units were activated exclusively by vestibular stimulation (unimodal vestibular units) and 16 units were activated by at least one other stimulus modality (multimodal vestibular units, Table 1). High-intensity vestibular stimulation was required to activate five of the unimodal vestibular and 10 of the multimodal vestibular units. Vestibular-activated units were found throughout the PO and the intralaminar nuclei and in the border region between the VPL and other thalamic nuclei (Fig. 2). Fourteen units (10%) responded to either electrical stimulation of the
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FIG. 1. Drawings of cross sections through the diencephalon at four positions. Section in A is most rosttal and D is most caudal. Each vertical line represents one electrode tract and the symbols represent the position of 334 neurons. VPL-ventral posterolateraf nucleus, VPM-ventral posteromedial nucleus, VL-ventral lateral nucleus, CL-central lateral nucleus, LP--lateral posterior nucleus, MG-medial geniculate nucleus, mcMGmagnocellular division of MG.
cochlear nerve or to sound. Four units showed a unimodal auditory response and all these units were in the medial geniculate nucleus. Ten units showed multimodal auditory responses and were in the PO (Fig. 2). One hundred twenty-two units (90% of responsive units) could be
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1
Units Classified by Type of Response to Sensory Stimulation Unimodal units Vestibular (low-intensity stimulation) Vestibular (high-intensity stimulation) Auditory Somatic Narrow-field Wide-field
1 5 4 66 41
Multimodal units Vestibular-somatic Vestibular-auditory Auditory-somatic Vestibular-auditory-somatic
activated by somatic stimuli. Sixty-six of these units were unimodal and had a receptive field on the face or on one limb of the contralateral side. These were termed “narrow-field” units and were in the central region of the VPL and ventral posteromedial nucleus. Thirty-seven narrow-field units were activated by electrical stimulation of the contralateral forepaw. A histogram of the distribution of the initial spike latency for these neurons is shown in Fig. 4A. Forty-one unimodal somatosensory units had bilateral receptive fields and were termed “wide-field” units. Fifteen units activated by somatic stimuli showed multimodal responses (Table 1). Both multimodal somatosensory and wide-field units were found in the PO, the intralaminar nuclei, and near the border between the VPL, the ventral posteromedial, and other thalamic nuclei (Fig. 2). A histogram is shown in Fig. 4B of the initial spike latency for 24 unimodal wide field units and seven multimodal somatosensory units that were activated by contralateral forepaw stimulation. DISCUSSION The present study was designed to identify and characterize the thalamic neurons activated by vestibular stimulation. Studies utilizing evoked potential and anatomic techniques have shown that the ventral, posterior, and intralaminar groups of nuclei may receive ascending vestibular activity (I, 7,9, 16,20). We found that 16% of the thalamic neurons responsive to sensory stimulation reacted to electrical stimulation of the vestibular nerve. Many of these neurons were activated by vestibular stimulation at short latencies, and six units showed unimodal vestibular responses. Units responding at short latencies to vestibular stimulation and unimodal vestibular units were located throughout the recording region and were not
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VESTIWLAR lUDlTORY SOWTIC
vxrcw
field
SOMATC-
aids fleld
FIG. 2. Sites of 136 neurons that were responsive to sensory stimuli. Remaining labels as in Fig. 1.
contained in any clearly demarcated anatomic zone. The initial spike latency to vestibular stimulation of unimodal vestibular units spanned a wide range. It has been proposed that the ascending vestibular pathway consists of neurons that respond to both vestibular and joint proprioceptive stimuli (11). This idea was not supported by the results of the present investigation or by other recent studies of vestibular-activated neurons in the thalamus (6, 15), or cerebral cortex (8, 19). The results of the present study indicate
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AND GILMAN
A . .
.
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. . . .
.
. . . . . . . . . . . . . . . . .
.
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. . . . . . . . . . .
.
.
.
. . . . . . l *
. .
FIG. 3. Responses of two units to low-intensity vestibular nerve stimulation at 0.3 Hz. Raster display represents a single spike as a dot and stores repetitive trials one below the other. Time calibration is 5 ms.
that vestibular-activated neurons in the thalamus of the cat form a single functional group and that these neurons show a high degree of convergence of sensory information, a broad range of initial spike latencies after vestibular nerve stimulation, and a distribution in the thalamus that includes the PO, the intralaminar nuclei, and a border region between the PO and the VPL. Somatosensory stimuli activated the majority of responsive neurons in this investigation. As in other studies of somatic-activated neurons in the thalamus, we identified three types of neurons, two of which responded exclusively to somatic stimuli. Narrow-field unimodal neurons had small contralateral receptive fields and were activated at short latency by peripheral stimulation. They were found chiefly in the VPL and ventral posteromedial nuclei. A second group, unimodal wide-field units, had
351
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a. f i
B.
” I t ‘de I
0
MULTIMOOAL
SOMATIC
n
WIDE-FELD
SOMATIC
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UNMDDAL
VE!STIBUAR
0
MULTIMODAL
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0
MULTIMODAL
VESTIBULAR
l-l
c. (I-#
IO
20 30 INITIAL SPIKE LATENCY
40
(high intensity)
50
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FIG. 4. A, B-histograms of the first spike latency of somatic-activated units to electrical stimulation of the contralateral forepaw (bin size = 2 ms). C-histogram of the initial spike latency of vestibular-activated neurons to electrical stimulation of the vestibular nerve (bin size = 2 ms).
bilateral peripheral receptive fields. These neurons were found in the ventral, intralaminar, and posterior groups of nuclei. Although some investigators have denied the existence of wide-field units in the primary sensory relay nuclei (3, 18) and sensory cortex (17), others have found wide-field units in the dorsal column nuclei (5), the VPL (12, 14), and the primary sensory cortex (21). In the present study both wide-field and
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narrow-field units were found in the VPL but were located in different regions of that nucleus. Narrow-field units were concentrated in the central region of the VPL. Some wide-field units were found in the regions surrounding the narrow-field units, but most were found in the PO. The third group of somatic-activated units was multimodal. These neurons were similar to the wide-field units with respect to their locations in the thalamus and distributions of initial spike latencies. There were marked similarities between the neurons activated by vestibular nerve stimulation and those characterized as wide-field and multimodal somatic neurons. First, 12 of the vestibular-activated neurons also were activated by somatic stimulation and consequently were included in the multimodal somatic group. Second, wide-field and multimodal somatic neurons and vestibular-activated neurons were found in a common region of thalamus: the PO, the intralaminar nuclei, and the border of the VPL. Third, the distribution of initial spike latencies after vestibular nerve stimulation was similar to the distribution of initial spike latencies of wide-field and multimodal somatic neurons after contralateral forepaw stimulation (Figs. 4B, C). Both these distributions clearly were different from the distribution of the initial spike latencies of the narrow-field neurons after stimulation (Fig. 4A). It appears, therefore, that the vestibular-activated thalamic neurons are similar to wide-field and multimodal somatic neurons and possibly are a subgroup of them. These data can be used to contrast the processing of vestibular information with other sensory information by the thalamus. It is well known that the thalamus contains “specific sensory nuclei” for auditory (medial geniculate nucleus), visual (lateral geniculate nucleus), and somatic (ventral basal complex) information (2,4, 13, 18). The neurons in these nuclei have restricted peripheral receptive fields, a rapidly conducting pathway from the periphery, and somatotopic, tonotopic, or retinotopic organization. The ability of the central nervous system to perceive details in the environment is attributed to activity ascending to the cortex after a relay in the specific sensory nuclei (18). Information from receptors is processed also in nuclei of the thalamus such as the PO having an organization different from that of the specific nuclei. In the PO there are neurons with large receptive fields, convergence of multiple modalities, and a slowly conducting pathway between the periphery and thalamus. Perceptions resulting from the cortical projections of these nuclei are thought to be characterized in terms of “general sensory awareness” rather than awareness of a specific stimulus (18). The vestibular system appears to be an exception to this organization, for despite numerous investigations, no specific sensory nuclei for vestibular activated neurons
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in thalamus have been found (6, 15). The population of vestibular-activated neurons in the thalamus is relatively homogenous and is characterized by multimodal convergence, an asynchrous discharge after vestibular stimulation, and a widespread distribution. REFERENCES 1. ABRAHAM, L., P. COPACK, AND S. GILMAN. 1977. Brain stem pathways for vestibular projections to cerebral cortex in the cat. Exp. Neurol. 55: 436-448. 2. AITKIN, L. M., AND W. R. WEBSTER. 1972. Medial geniculate body of the cat: organization and responses to tonal stimuli of neurons in ventral division. J. Neurophysiol. 35: 365-380. 3. ANDERSON, P., J. C. ECCLES, R. F. SCHMIDT, AND T. YOKOTA. 1964. Identification of relay cells and interneurons in the cuneate nucleus. J. Neurophysiol. 27: 1080- 1095. 4. BERKLEY, K. J. 1973. Response properties of cells in ventrobasal and posterior group nuclei of the cat. J. Neurophysiol. 36: 940-952. 5. BLUM, P., M. B. BROMBERG, AND D. WHITEHORN. 1975. Population analysis of single units in the cuneate nucleus of the cat. Exp. Neural. 48: 57-78. 6. BLUM, P. S., L. ABRAHAM, AND S. GILMAN. 1979. Vestibular, auditory, and somatic input to posterior thalamus. Exp. Brain Res. 34: l-9. 7. BLUM, P. S., M. J. DAY, M. B. CARPENTER, AND S. GILMAN. 1979. Thalamic components of the ascending vestibular system. Exp. Neural. 8. BOISACQ-SCHEPENS, N., AND M. HANUS. 1972. Motor cortex vestibular responses in the chloralosed cat. Exp. Brain Res. 14: 539-549. 9. COPACK, P., N. DAFNY, AND S. GILMAN. 1972. Neurophysiological evidence of vestibular projection to thalamus, basal ganglia, and cerebral cortex. Pages 309-339in T.L. FRIGYESI, E. RINVIK, AND M. D. YAHR, Eds., Corticothalamic Projections and Sensorimotor Activities. Raven Press, New York. AND J. M. FREDRICKSON. 1974. Nucleus 10. DEECKE, L., D. W. F. SCHWARZ, ventroposterior inferior (VPI) as the vestibular thalamic relay in the rhesus monkey. Exp. Brain Res. 20: 88-100. 11. FREDRICKSON, J. M., H. H. KORNHUBER, AND D. W. F. SCHWARZ. 1974. Cortical projections of the vestibular nerve. Pages 565-582 in H. H. KORNHUBER, Ed., Handbook of Sensory Physiology, Vol. VI/l. Springer Verlag, Berlin. 12. HARRIS, F. A. 1970. Population analysis of somatosensory thalamus in the cat. Nature (London) 225: 559-562. 13. HUBEL, D. H., AND T. N. WIESEL. l%l. Integrative action in the cat’s lateral geniculate body. .I. Physiol. (London) 155: 385-398. 14. JABBUR, S. J., M. A. BAKER, AND A. L. TOWE. 1972. Wide-field neurons in nucleus ventralis posterolateralis of the cat. Exp. Neural. 36: 213-238. 15. LIEDGREN, S. R. C., A. C. MILNE, A. M. RUBIN, D. W. F. SCHWAIU, AND R. D. TOMLINSON. 1976. Representation of vestibular aRerents in somatosensory thalamic nuclei of the squirrel monkey (Sarmiri sciureus). J. Neurophysiol. 39: 601-612. 16. MICKLE, W. A., AND H. W. ADES. 1954. Rostral projection pathway of the vestibular system. Am. J. Physiol. 176: 243-246, 17. MOUNTCASTLE, V. B. 1957. Modality and topographic properties of single neurons in cat’s somatic sensory cortex. J. Neurophysiol. 20: 408-434. 18. POGGIO, G. F., AND V. B. MOUNTCASTLE. 1957. A study ofthe functional contributions of
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the lemniscal and spinothalamic systems to somatic sensibility. Bull. Johns Hopkins Hosp. 106: 266-316. 19. ~DKVIST, L. M., S. R. C. LIEDGREN, B. LARSBY, AND L. JERLVALL. 1975. Vestibularand somatosensory inflow to the vestibular projection area in the post cruciate dimple region of the cat cerebral cortex. Exp. Brain Res. 22: 185-196. 20. ROLJCOLJX-HANUS,M., AND N. BOISACQ-SCHEPENS. 1977. Ascending vestibular projections: further results at cortical and thalamic levels in the cat. Ecp. Bruin Res. 29: 283-292.
21. TOWE, A. L. 1968. Neuronal population behavior in the somatosensory systems. Pages 552-574in D. R. KENSHALO, Ed., The Skin Senses. Charles C Thomas, Springfield, Ill.
Vestibular,
NEUROLOGY
65, 343-354
Somatosensory, Thalamus P.
Department of Neurology, York, New York 10032,
S. BLUM
(1979)
and Auditory of the Cat AND
Input to the
S. GILMAN’
College of Physicians and Surgeons, Columbia University, New and Department of Physiology, Thomas Jefferson University, Philadelphia. Pennsylvania 19107
Received
March
5, 1979
Responses were recorded and analyzed for 334 single units in the ventral, posterior, and intralaminar groups of thalamic nuclei of the cat. Units were tested for a response after (i) electrical stimulation of the vestibular nerve; (ii) electrical stimulation of the four paw pads and natural stimulation of joint, muscle, and cutaneous receptors of the limbs, trunk, and head (somatic stimulation); and (iii) electrical stimulation of the cochlear nerve and sound (auditory stimuli). Forty-one percent of the units responded to these stimuli. Vestibular stimulation activated 16% of the responsive units. These units were found primarily in the posterior nucleus and the border region between it and the ventral posterolateral nucleus. Seventy-three percent of vestibular-activated units also responded to at least one other modality of sensory stimuli. No evidence was found for a thalamic region where the majority of units responded at short latency to vestibular nerve stimulation. Ninety percent of the responsive units were activated by somatic stimuli. These units could be divided into two groups. One group was composed of units that were activated exclusively by somatic stimuli and had a small contralateral receptive field. These units were found primarily in the ventral posterolateral nucleus. The other group had a bilateral receptive field or was activated by more than one modality of sensory stimuli. These units were. found primarily in the posterior nucleus and the border area of the ventral posterolateral nucleus. Units that responded to auditory stimulation (10% of responsive units) were found in the posterior nucleus and the medial geniculate nucleus. Abbreviations: VPL-ventral posterolateral nucleus, PO-posterior nucleus. 1 Partially supported by U.S. Public Health Service grant NSll307. The present address of Dr. Blum is Department of Physiology, Thomas Jefferson University and that of Dr. Oilman is Department of Neurology, University of Michigan, Ann Arbor, MI 48109.
343 0014-4886/79/080343-12$02.00/O Copyright 0 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
344
BLUM
AND
GILMAN
INTRODUCTION Several investigators have used evoked potential techniques to explore the thalamic projections of the ascending components of the vestibular system (1, 7, 9, 16, 20). In a recent study, Blum et al. (7) used these techniques to survey the thalamic nuclei that had been shown, in separate anatomical experiments, to contain neurons projecting to the vestibular receiving regions of the cerebral cortex. Short-latency (~3.5 ms) and high-amplitude evoked potentials were found in the ventral posterolateral nucleus (VPL) and the rostra1 part of the posterior nucleus (PO). It was concluded that neurons in VPL and the rostra1 part of PO constitute an important component of the thalamic nuclei that relay vestibular activity to the cerebral cortex at short latency. Although valuable, evoked potential studies have the shortcomings that their precise localizing value is limited and the responsiveness of individual neurons to vestibular and other modalities of stimulation cannot be determined. The issue of the responsiveness to various modalities of stimulation of vestibular-activated neurons in the thalamus is important because the auditory and somatosensory systems have a strong representation in the region of the thalamus showing vestibular-evoked potentials (2, 4, 18). Thus far, only two studies have been made of the responses of single thalamic neurons to vestibular nerve stimulation. In the squirrel monkey, Liedgren et al. (15) examined the responses to sensory stimuli of single neural units in the ventral, posterior, and intralaminar groups of nuclei. They found vestibular-activated neurons throughout the region investigated. More than 60% of vestibular-activated neurons also responded to somatosensory or auditory stimuli. Evoked potential studies of the ascending vestibular system projections in the monkey, however, showed that large-amplitude responses are in a region different from that in the cat (10). There is only one study of thalamic unit responses to vestibular and other stimuli in the cat. Blum et al. (6) recorded the responses of neurons in the posterior portion of the PO to auditory and somatosensory stimuli. They found that only 5% of the neurons were activated by vestibular nerve stimulation. These neurons showed long-latency responses to vestibular stimulation and multimodal responses, including vestibular, auditory, and somatosensory stimuli. These neurons were outside the region containing large-amplitude, short-latency vestibular evoked potentials. Consequently, these data represent only a partial characterization of the thalamic nuclei involved in the processing of ascending vestibular activity. The present studies were designed to use single-unit recordings for determining the responses of single thalamic neurons to vestibular and other modalities of stimulation. The data show that vestibular-activated
SENSORY
INPUT
TO THALAMUS
345
neurons are situated in the PO and in the border between the PO and the VPL and that most of these neurons also respond to somatosensory and/or auditory stimulation. METHODS Adult cats weighing between 2.0 and 3.5 kg were anesthetized with alpha-chloralose (60 mg/kg, i.v.). Cannulas were placed in the trachea and in a femoral vein and artery. The blood pressure was maintained above 90 mm Hg with 6% dextran in saline, if necessary, and the body temperature was maintained at 37°C with a thermostatically controlled heating pad. The animals were paralyzed with gallamine triethiodide (Flaxedil) and respired artificially during recording. A bipolar electrode was placed on the right vestibular nerve, and a second electrode was placed on the right cochlear nerve. Stimulation was applied through the electrode on the vestibular nerve with a 0. 1-ms pulse. Stimulus intensity was adjusted during recordings of averaged potentials from electrodes in the lateral vestibular and dorsal cochlear nuclei. The intensity was set in each experiment so that fibers of the vestibular nerve were excited but fibers in the nearby cochlear nerve were not affected (low-intensity vestibular stimulation). The procedure to determine the value for low intensity vestibular stimulation was described previously (1, 6,7,9). The stimulus intensity of a O.l-ms pulse delivered to the cochlear nerve was adjusted in an analogous manner. In some experiments, the effect of low-intensity vestibular stimulation was monitored with a monopolar electrode on the vestibular projection area of the cerebral cortex. Recordings were obtained from the cerebral cortex to show that the ascending vestibular pathway was active during the experiments. Natural stimulation was used to assess unit responsiveness to stimulation of joint, muscle, and cutaneous receptors of the limbs and trunk (somatosensory stimuli). Flexion and extension of the joints of all four limbs and the vertebral column were used forjoint and muscle stimulation. Blowing and light brushing across the fur of the limbs, face, and trunk were used for cutaneous stimulation. Sound (clicks, hand claps) was used to stimulate the cochlear receptors. Electrical stimulation was applied to the paw pads through needle electrodes placed on either side of the central portion of the paw. Stimuli consisted of 0. I-ms square wave pulses at 10 V. The activity of single neural units was recorded in the thalamus with glass microelectrodes filled with either 2 M NaCl saturated with fast green dye or 2 M NaCl. Standard amplification and display techniques were used. Stimulation of the vestibular nerve at 0.3 Hz was used as a “hunting” stimulus as the recording electrode was advanced into the thalamus. To
346
BLUMANDGILMAN
ensure that neural units responsive to vestibular stimulation would be found, the intensity of vestibular nerve stimulation was set at 5 to 10 times the low-intensity vestibular stimulation value (high-intensity vestibular stimulation). Units responsive to high-intensity vestibular stimulation and those showing activity without overt stimulation (spontaneous activity) were recorded and analyzed. Each unit was tested with a standard battery of stimuli, including (i) vestibular nerve electrical stimulation at 0.3 Hz, both high- and low-intensity; (ii) electrical stimulation of the cochlear nerve at 0.3 Hz; (iii) natural auditory stimulation; and (iv) somatic stimulation. Units were considered responsive to an electrical stimulus if a stimuluslocked response occurred in at least 50% of the 16 to 32 stimulus trials. The responsiveness of each unit to the natural stimuli was assessed by observing its activity with an oscilloscope and an audio monitor before, during, and after stimulation. On completion of each electrode penetration, a small fast green mark or electrolytic lesion was made at the bottom of the track by passing 5 to 20 PA current with the electrode negative for 5 to 10 min. The site of recording of each unit was determined by the stereotaxic parameters taken at the time of recording and subsequent histological examination of the tissue. RESULTS The activity of 334 units was recorded during 54 electrode penetrations through the thalamus. Forty-one percent (136) of the units responded to one or more of the stimuli. Units unresponsive to the stimuli were found throughout the thalamus, often adjacent to responsive units in a single electrode penetration (Fig. 1). Some units were responsive only to one modality of stimuli and are termed “unimodal.” Other units responded to more than one modality and are termed “multimodal.” Table 1 contains a summary of the different groups of units based upon their responses to vestibular, auditory, and somatic stimuli. Vestibular stimulation activated 16% (22) of the responsive units (Fig. 2). The responses of two units to vestibular stimulation are shown in Fig. 3. The latencies of the initial spike after vestibular stimulation for all vestibular-activated units were from 4 to 24 ms (Fig. 4C). Six units were activated exclusively by vestibular stimulation (unimodal vestibular units) and 16 units were activated by at least one other stimulus modality (multimodal vestibular units, Table 1). High-intensity vestibular stimulation was required to activate five of the unimodal vestibular and 10 of the multimodal vestibular units. Vestibular-activated units were found throughout the PO and the intralaminar nuclei and in the border region between the VPL and other thalamic nuclei (Fig. 2). Fourteen units (10%) responded to either electrical stimulation of the
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347
FIG. 1. Drawings of cross sections through the diencephalon at four positions. Section in A is most rosttal and D is most caudal. Each vertical line represents one electrode tract and the symbols represent the position of 334 neurons. VPL-ventral posterolateraf nucleus, VPM-ventral posteromedial nucleus, VL-ventral lateral nucleus, CL-central lateral nucleus, LP--lateral posterior nucleus, MG-medial geniculate nucleus, mcMGmagnocellular division of MG.
cochlear nerve or to sound. Four units showed a unimodal auditory response and all these units were in the medial geniculate nucleus. Ten units showed multimodal auditory responses and were in the PO (Fig. 2). One hundred twenty-two units (90% of responsive units) could be
348
BLUM AND GILMAN TABLE
1
Units Classified by Type of Response to Sensory Stimulation Unimodal units Vestibular (low-intensity stimulation) Vestibular (high-intensity stimulation) Auditory Somatic Narrow-field Wide-field
1 5 4 66 41
Multimodal units Vestibular-somatic Vestibular-auditory Auditory-somatic Vestibular-auditory-somatic
activated by somatic stimuli. Sixty-six of these units were unimodal and had a receptive field on the face or on one limb of the contralateral side. These were termed “narrow-field” units and were in the central region of the VPL and ventral posteromedial nucleus. Thirty-seven narrow-field units were activated by electrical stimulation of the contralateral forepaw. A histogram of the distribution of the initial spike latency for these neurons is shown in Fig. 4A. Forty-one unimodal somatosensory units had bilateral receptive fields and were termed “wide-field” units. Fifteen units activated by somatic stimuli showed multimodal responses (Table 1). Both multimodal somatosensory and wide-field units were found in the PO, the intralaminar nuclei, and near the border between the VPL, the ventral posteromedial, and other thalamic nuclei (Fig. 2). A histogram is shown in Fig. 4B of the initial spike latency for 24 unimodal wide field units and seven multimodal somatosensory units that were activated by contralateral forepaw stimulation. DISCUSSION The present study was designed to identify and characterize the thalamic neurons activated by vestibular stimulation. Studies utilizing evoked potential and anatomic techniques have shown that the ventral, posterior, and intralaminar groups of nuclei may receive ascending vestibular activity (I, 7,9, 16,20). We found that 16% of the thalamic neurons responsive to sensory stimulation reacted to electrical stimulation of the vestibular nerve. Many of these neurons were activated by vestibular stimulation at short latencies, and six units showed unimodal vestibular responses. Units responding at short latencies to vestibular stimulation and unimodal vestibular units were located throughout the recording region and were not
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FIG. 2. Sites of 136 neurons that were responsive to sensory stimuli. Remaining labels as in Fig. 1.
contained in any clearly demarcated anatomic zone. The initial spike latency to vestibular stimulation of unimodal vestibular units spanned a wide range. It has been proposed that the ascending vestibular pathway consists of neurons that respond to both vestibular and joint proprioceptive stimuli (11). This idea was not supported by the results of the present investigation or by other recent studies of vestibular-activated neurons in the thalamus (6, 15), or cerebral cortex (8, 19). The results of the present study indicate
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FIG. 3. Responses of two units to low-intensity vestibular nerve stimulation at 0.3 Hz. Raster display represents a single spike as a dot and stores repetitive trials one below the other. Time calibration is 5 ms.
that vestibular-activated neurons in the thalamus of the cat form a single functional group and that these neurons show a high degree of convergence of sensory information, a broad range of initial spike latencies after vestibular nerve stimulation, and a distribution in the thalamus that includes the PO, the intralaminar nuclei, and a border region between the PO and the VPL. Somatosensory stimuli activated the majority of responsive neurons in this investigation. As in other studies of somatic-activated neurons in the thalamus, we identified three types of neurons, two of which responded exclusively to somatic stimuli. Narrow-field unimodal neurons had small contralateral receptive fields and were activated at short latency by peripheral stimulation. They were found chiefly in the VPL and ventral posteromedial nuclei. A second group, unimodal wide-field units, had
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FIG. 4. A, B-histograms of the first spike latency of somatic-activated units to electrical stimulation of the contralateral forepaw (bin size = 2 ms). C-histogram of the initial spike latency of vestibular-activated neurons to electrical stimulation of the vestibular nerve (bin size = 2 ms).
bilateral peripheral receptive fields. These neurons were found in the ventral, intralaminar, and posterior groups of nuclei. Although some investigators have denied the existence of wide-field units in the primary sensory relay nuclei (3, 18) and sensory cortex (17), others have found wide-field units in the dorsal column nuclei (5), the VPL (12, 14), and the primary sensory cortex (21). In the present study both wide-field and
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narrow-field units were found in the VPL but were located in different regions of that nucleus. Narrow-field units were concentrated in the central region of the VPL. Some wide-field units were found in the regions surrounding the narrow-field units, but most were found in the PO. The third group of somatic-activated units was multimodal. These neurons were similar to the wide-field units with respect to their locations in the thalamus and distributions of initial spike latencies. There were marked similarities between the neurons activated by vestibular nerve stimulation and those characterized as wide-field and multimodal somatic neurons. First, 12 of the vestibular-activated neurons also were activated by somatic stimulation and consequently were included in the multimodal somatic group. Second, wide-field and multimodal somatic neurons and vestibular-activated neurons were found in a common region of thalamus: the PO, the intralaminar nuclei, and the border of the VPL. Third, the distribution of initial spike latencies after vestibular nerve stimulation was similar to the distribution of initial spike latencies of wide-field and multimodal somatic neurons after contralateral forepaw stimulation (Figs. 4B, C). Both these distributions clearly were different from the distribution of the initial spike latencies of the narrow-field neurons after stimulation (Fig. 4A). It appears, therefore, that the vestibular-activated thalamic neurons are similar to wide-field and multimodal somatic neurons and possibly are a subgroup of them. These data can be used to contrast the processing of vestibular information with other sensory information by the thalamus. It is well known that the thalamus contains “specific sensory nuclei” for auditory (medial geniculate nucleus), visual (lateral geniculate nucleus), and somatic (ventral basal complex) information (2,4, 13, 18). The neurons in these nuclei have restricted peripheral receptive fields, a rapidly conducting pathway from the periphery, and somatotopic, tonotopic, or retinotopic organization. The ability of the central nervous system to perceive details in the environment is attributed to activity ascending to the cortex after a relay in the specific sensory nuclei (18). Information from receptors is processed also in nuclei of the thalamus such as the PO having an organization different from that of the specific nuclei. In the PO there are neurons with large receptive fields, convergence of multiple modalities, and a slowly conducting pathway between the periphery and thalamus. Perceptions resulting from the cortical projections of these nuclei are thought to be characterized in terms of “general sensory awareness” rather than awareness of a specific stimulus (18). The vestibular system appears to be an exception to this organization, for despite numerous investigations, no specific sensory nuclei for vestibular activated neurons
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in thalamus have been found (6, 15). The population of vestibular-activated neurons in the thalamus is relatively homogenous and is characterized by multimodal convergence, an asynchrous discharge after vestibular stimulation, and a widespread distribution. REFERENCES 1. ABRAHAM, L., P. COPACK, AND S. GILMAN. 1977. Brain stem pathways for vestibular projections to cerebral cortex in the cat. Exp. Neurol. 55: 436-448. 2. AITKIN, L. M., AND W. R. WEBSTER. 1972. Medial geniculate body of the cat: organization and responses to tonal stimuli of neurons in ventral division. J. Neurophysiol. 35: 365-380. 3. ANDERSON, P., J. C. ECCLES, R. F. SCHMIDT, AND T. YOKOTA. 1964. Identification of relay cells and interneurons in the cuneate nucleus. J. Neurophysiol. 27: 1080- 1095. 4. BERKLEY, K. J. 1973. Response properties of cells in ventrobasal and posterior group nuclei of the cat. J. Neurophysiol. 36: 940-952. 5. BLUM, P., M. B. BROMBERG, AND D. WHITEHORN. 1975. Population analysis of single units in the cuneate nucleus of the cat. Exp. Neural. 48: 57-78. 6. BLUM, P. S., L. ABRAHAM, AND S. GILMAN. 1979. Vestibular, auditory, and somatic input to posterior thalamus. Exp. Brain Res. 34: l-9. 7. BLUM, P. S., M. J. DAY, M. B. CARPENTER, AND S. GILMAN. 1979. Thalamic components of the ascending vestibular system. Exp. Neural. 8. BOISACQ-SCHEPENS, N., AND M. HANUS. 1972. Motor cortex vestibular responses in the chloralosed cat. Exp. Brain Res. 14: 539-549. 9. COPACK, P., N. DAFNY, AND S. GILMAN. 1972. Neurophysiological evidence of vestibular projection to thalamus, basal ganglia, and cerebral cortex. Pages 309-339in T.L. FRIGYESI, E. RINVIK, AND M. D. YAHR, Eds., Corticothalamic Projections and Sensorimotor Activities. Raven Press, New York. AND J. M. FREDRICKSON. 1974. Nucleus 10. DEECKE, L., D. W. F. SCHWARZ, ventroposterior inferior (VPI) as the vestibular thalamic relay in the rhesus monkey. Exp. Brain Res. 20: 88-100. 11. FREDRICKSON, J. M., H. H. KORNHUBER, AND D. W. F. SCHWARZ. 1974. Cortical projections of the vestibular nerve. Pages 565-582 in H. H. KORNHUBER, Ed., Handbook of Sensory Physiology, Vol. VI/l. Springer Verlag, Berlin. 12. HARRIS, F. A. 1970. Population analysis of somatosensory thalamus in the cat. Nature (London) 225: 559-562. 13. HUBEL, D. H., AND T. N. WIESEL. l%l. Integrative action in the cat’s lateral geniculate body. .I. Physiol. (London) 155: 385-398. 14. JABBUR, S. J., M. A. BAKER, AND A. L. TOWE. 1972. Wide-field neurons in nucleus ventralis posterolateralis of the cat. Exp. Neural. 36: 213-238. 15. LIEDGREN, S. R. C., A. C. MILNE, A. M. RUBIN, D. W. F. SCHWAIU, AND R. D. TOMLINSON. 1976. Representation of vestibular aRerents in somatosensory thalamic nuclei of the squirrel monkey (Sarmiri sciureus). J. Neurophysiol. 39: 601-612. 16. MICKLE, W. A., AND H. W. ADES. 1954. Rostral projection pathway of the vestibular system. Am. J. Physiol. 176: 243-246, 17. MOUNTCASTLE, V. B. 1957. Modality and topographic properties of single neurons in cat’s somatic sensory cortex. J. Neurophysiol. 20: 408-434. 18. POGGIO, G. F., AND V. B. MOUNTCASTLE. 1957. A study ofthe functional contributions of
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the lemniscal and spinothalamic systems to somatic sensibility. Bull. Johns Hopkins Hosp. 106: 266-316. 19. ~DKVIST, L. M., S. R. C. LIEDGREN, B. LARSBY, AND L. JERLVALL. 1975. Vestibularand somatosensory inflow to the vestibular projection area in the post cruciate dimple region of the cat cerebral cortex. Exp. Brain Res. 22: 185-196. 20. ROLJCOLJX-HANUS,M., AND N. BOISACQ-SCHEPENS. 1977. Ascending vestibular projections: further results at cortical and thalamic levels in the cat. Ecp. Bruin Res. 29: 283-292.
21. TOWE, A. L. 1968. Neuronal population behavior in the somatosensory systems. Pages 552-574in D. R. KENSHALO, Ed., The Skin Senses. Charles C Thomas, Springfield, Ill.