172
Brain Research, 106 (1976) 172 175 ,C~ Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
Responses of extralemniscal thalamic neurones to stimulation of the fastigial nucleus and influences of the cerebral cortex in the cat
K U N I T A K A KITANO, YOSHITAKA ISHIDA, TOSHIO ISHIKAWA AND SATOSHI MURAYAMA
Department of Pharmacology, School of Medicine, and (T.I.) Department of Physiology and Biochemistry, School of Nursing, Chiba University, Chiba (Japan) (Accepted January 5th, 1976)
Intralaminar thalamic nuclei including the centromedian-parafascicular complex are thought to play an important role in the so-called extralemniscal sensory system. Many studies have reported, in the past decade, on intralaminar thalamic neurones, and electrophysiological properties of their responses to peripheral stimulation have been well studied by Alb6-Fessard and co-workers 7-9 and McKenzie et al. 10,11. Inhibitory and excitatory influences from different brain structures on intralaminar neurones have also been reported 3,1z,14. Although anatomical studies have revealed that efferent fibres originating in the cerebellar fastigial nucleus terminate in the intralaminar thalamic nuclei6, la. no electrophysiological study on the pathway has yet been reported. In the present experiments, the properties of unitary evoked responses of intralaminar thalamic neurones to electrical stimulation of the fastigial nucleus were studied. Effects of conditioning stimulation of the cerebral cortex on those responses were also investigated. Eighteen cats were anaesthetized with a-chloralose (50-80 mg/kg, i.v.), immobilized with gallamine triethiodide and artificially ventilated. Bipolar concentric steel electrodes were placed stereotaxically within the fastigial nucleus contralateral to the recorded thalamus and stimuli were applied with single pulses of 4-20 V intensity and 0.2 msec duration. The position of the electrode tip was histologically verified after the experiment. The exposed bilateral superficial radial nerves were mounted on bipolar silver-wire electrodes in a paraffin pool and were stimulated with single pulses of 0.5-3 V intensity and 0.2 msec duration. Pulses of intensity 2-10 V, 0.5 msec duration and a train of 5 stimuli at 250 Hz were applied to a pair of silverball electrodes laid on the anterior sigmoid gyrus ipsilateral to the thalamus recorded. The intralaminar thalamic neurones were located stereotaxically through the intact cortex and records were made extraceltularly by means of glass micropipettes containing 3 M KC! of 6-20 M ~ impedance. Intralaminar neurones responded to stimulation of each o f 4 extremities in a convergent manner with rather long response latencies around 25 msec (Fig. IA and
173
i,=,....a
0
JJJ
jl
i
i
_
~lllWliilllllltl
d Fig. 1. Responses of an intralaminar thalamic neurone to ipsilateral (A) and contralateral (B) superficial radial nerve stimulation with a typical response pattern of convergence. C: response of the same neurone as (A) and (B) to the contralateral fastigial stimulation. D: short and long latency responses to fastigial stimulation. E: spontaneous unit discharge of a thalamic neurone inhibited by a single shock to the fastigial nucleus. Calibrations: 20 msec for A, B and C; 50 msec for D and E; 5 mV amplitude. B). Moreover those responses were extremely weak to repetitive peripheral stimuli and rarely followed stimulation rates in excess of 8 Hz. These electrophysiological properties of intralaminar neuronal responses were in good accordance with results reported by other investigators7,10-12 and were quite useful in our experiments for the identification of intralaminar neurones responding to fastigial stimulation. A m o n g a total of 153 single units studied, 121 (79~o) units responded to all electrical stimulation of the fastigial nucleus and of the ipsi- and contralateral radial nerve (Fig. 1A-C). Six ( 4 ~ ) units responded only to fastigial stimulation and 26 (17 ~o) units responded only to peripheral stimulation. All the neurones studied were encountered within the stereotaxic limits: A 6.5-8.0, L 1.0-3.0, H + 3 . 0 to --2.0, and according to the histological reconstruction by electrode tracks they were located in nucleus centrum medianum and nucleus parafascicularis. In the present experiments, however, the following studies were made on units which responded both to fastigial and peripheral stimulation. In almost all cases, the spike discharges to fastigial stimulation were identical in shape and amplitude to those obtained following radial nerve stimulation. The response latencies for the first spike in a unit's discharge to fastigial stimulation ranged from 7 to 35 msec and the majority of units responded with latencies from 7 to 15 msec. The mean latency was calculated to be 12.9 msec and, assuming the fastigothalamic pathway to be monosynaptic, the conduction velocity of the fibres should be about 1.46 m/sec. Intralaminar neurones responded to repetitive stimulation of the fastigial nucleus up to 20 Hz without fail. Some neurones showed dual responses to fastigial stimulation at short and long latencies from 100 to 450 msec (Fig. I D). The analogous phenomenon was observed in the case of peripheral stimulation and was in accordance with the results reported by Alb6-Fessard and Kruger 4. Relatively
174
A
v
C
i
1
4.- ~ t r , , , r w ~ t -
]
I
I
Fig. 2. Inhibition and excitation of intralaminar unit responses following cortical stimulation. A unit with a burst of spikes to stimulation of the contralateral fastigial nucleus is shown in A, The response was inhibited by prior stimulation of the cerebral cortex (B). With increased cortical stimulus intensity excitation of the thalamic neurone followed by inhibition of subsequent fastigial response was observed (C), Calibration : 20 msec, 5 mV. few i n t r a l a m i n a r neurones discharged s p o n t a n e o u s l y u n d e r c h l o r a l o s e anaesthesia a n d they were in some cases inhibited for 200-300 msec following single shocks to fastigial nucleus (Fig. t E). The n e u r o n a l mechanism o f the inhibition r e m a i n s to be clarified. A b r i e f volley a p p l i e d to a n t e r i o r s i g m o i d gyrus 50 msec p r i o r to fastigial s t i m u l a t i o n inhibited 109 (90%) i n t r a l a m i n a r unitary responses e v o k e d by fastigial s t i m u l a t i o n (Fig. 2A and B). The r e m a i n i n g 12 units (10%) were not influenced. Effects o f cortical s t i m u l a t i o n on t h a l a m i c responses to fastigial s t i m u l a t i o n were e x a m i n e d at v a r i o u s c o n d i t i o n i n g test intervals. The intervals for onset o f inhibition r a n g e d from 15 to 20 msec and the interval for initial sign o f recovery r a n g e d f r o m 90 to 150 msec as shown in Fig. 3. In o u r e x p e r i m e n t s a c o n d i t i o n i n g test interval o f 50 msec was therefore chosen to e x a m i n e the effects o f cortical stimulation. In m a n y instances cortical s t i m u l a t i o n with stimulus intensities greater t h a n those required for inhibition p r o d u c e d e x c i t a t o r y responses followed by inhibition o f
I00
/
"-i
80 60 40 20
0
20
40
60
80
I00
120
140
160
rllsec
Fig. 3. Time course of cortical inhibition of a thalamic response to fastigial stimulation. Number of spikes as a percentage of t h a t of control response (ordinate) is plotted against interval between conditioning and test stimulation (abscissa). At least 5 conditioning-test interactions were observed at each interval, interspersed with test fastigial stimuli alone.
175 i n t r a l a m i n a r n e u r o n e s r e s p o n d i n g to fastigial s t i m u l a t i o n (Fig. 2C), The responses driven by the cortical volley seemed to be excitatory synaptic ones as they did n o t have fixed response latency, having only 2 or 3 spikes to a t r a i n of 5 stimuli a n d interspike intervals were i n c o n s t a n t in each trial. These excitatory spikes produced by cortical s t i m u l a t i o n were also observed by Albd-Fessard a n d Gillett 2 a n d AlbGFessard et al. 1, who investigated the effects of cortical s t i m u l a t i o n on i n t r a l a m i n a r n e u r o n e s r e s p o n d i n g to peripheral stimulation. The present experiments revealed some electrophysiological properties of the fastigothalamic p a t h w a y ; n o t only afferent i n f o r m a t i o n from each of extremities b u t also cerebellar impulses from the fastigial nucleus 'converge' to the i n t r a l a m i n a r t h a l a m i c neurones. Both excitatory and i n h i b i t o r y influences exerted by cortical s t i m u l a t i o n on i n t r a l a m i n a r n e u r o n e s r e s p o n d i n g to fastigial s t i m u l a t i o n suggest an i n v o l v e m e n t of the cerebral cortex in m o d u l a t i o n of cerebellar i n p u t to the i n t r a l a m i n a r thalamus. We are grateful to Prof. K l a u s R. U n n a for a critical reading of the m a n u s c r i p t , Mr. Masaji T a m a g a w a for electrotechnical assistance in the course of this work a n d Mr. Isao S a k u r a d a for p r e p a r i n g the photographs.
1 ALBI~-FESSARD,D., ]~ESSON,J. M., GUILBAUD,G., AND LEVANTE,A., Cortical control of somatic inflow to medial thalamus. In T. L. FRIGYESI,E. RINVIK AND M. D. YAHR (Eds.), Corticotha/amic Projections and Sensorimotor Activities, Raven Press, New York, 1972, pp. 283-303. 2 ALBI~-FESSARD,D., ET GILLETT,E., Convergences d'affGrences d'origines corticale et pGriphGrique vers le centre mGdian du chat anesthGsi6 ou 6veillG, Electroenceph. clin. Neurophysiol., 13 (1961) 257 269. 3 ALB~,-UESSARD,D., AND KRAUTHAMER,G., Inhibition of units of the non-specific afferent system by stimulation of the basal ganglia, J. Physiol. (Lond.), 175 (1964) 54P-55P. 4 ALB~-FESSARD,D., AND KRUGER, L., Duality of unit discharges from cat centrum medianum in response to natural and electrical stimulation, J. Neurophysiol., 25 (1962) 3-20. 5 CARPENTER,M. B., BARD, D. S., AND ALLING, F. A., Anatomical connections between the fastigial nuclei, the labyrinth and the vestibular nuclei in the cat, J. comp. Neurol., 111 (1959) 1 25. 6 CARPENTER,M. B., BRITTIN,G. M., ArqDPINES, J., Isolated lesions of the fastigial nuclei in the cat, J. comp. Neurol., 109 (1958) 65 89. 7 FELTZ, P., KRAUTHAMER,G., AND ALB~-FESSARO,D., Neurons of the medial diencephalon. 1. Somatosensory responses and caudate inhibition, J. Neurophysiol., 30 (1967) 55-80. 8 KRAUTHAMER,G., AND ALB~-FESSARD,D., Inhibition of nonspecific sensory activities follov,,ing striopallidal and capsular stimulation, J. Neurophysiol., 28 (1965) 100-124. 9 KRUGER,L., AND ALB~-FESSARD,D., Distribution of responses to somatic afferent stimuli in the diencephalon of the cat under chloralose anesthesia, Exp. Neurol., 2 (1960) 442 467. 10 MCKENZIE,J. S., AND GILBERT,D. M., Hippocampal and neostriatal inhibition of medial thalamic unit responses to somatic and brain stem stimulation, Brain Research, 38 (1972) 202-205. 11 MCKENZtE,J. S., GILBERT,D. M., AND ROGERS, D. K., Hippocampal and neostriatal inhibition of extralemniscal thalamic unitary responses in the cat, Brain Research, 27 (1971) 382 385. 12 McKENzlE, J. S., AND ROGERS, D. K., Hippocampal suppression of intralaminar thalamic unit responses in cats and comparison with suppression evoked from the caudate nucleus, Brain Research, 64 (1973) 1-15. 13 PROaST, M., Zur Anatomie und Physiologie des Kleinhirns, Arch. Psychiat. (Nervenkr.), 35 (1902) 692 777. 14 ROGERS, D. K., AND MCKENZIE,J. S., Regional differences within the caudate nucleus for suppression of extralemniscal thalamic units, Brain Research, 56 (1973) 345 349.
Brain Research, 106 (1976) 172 175 ,C~ Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
Responses of extralemniscal thalamic neurones to stimulation of the fastigial nucleus and influences of the cerebral cortex in the cat
K U N I T A K A KITANO, YOSHITAKA ISHIDA, TOSHIO ISHIKAWA AND SATOSHI MURAYAMA
Department of Pharmacology, School of Medicine, and (T.I.) Department of Physiology and Biochemistry, School of Nursing, Chiba University, Chiba (Japan) (Accepted January 5th, 1976)
Intralaminar thalamic nuclei including the centromedian-parafascicular complex are thought to play an important role in the so-called extralemniscal sensory system. Many studies have reported, in the past decade, on intralaminar thalamic neurones, and electrophysiological properties of their responses to peripheral stimulation have been well studied by Alb6-Fessard and co-workers 7-9 and McKenzie et al. 10,11. Inhibitory and excitatory influences from different brain structures on intralaminar neurones have also been reported 3,1z,14. Although anatomical studies have revealed that efferent fibres originating in the cerebellar fastigial nucleus terminate in the intralaminar thalamic nuclei6, la. no electrophysiological study on the pathway has yet been reported. In the present experiments, the properties of unitary evoked responses of intralaminar thalamic neurones to electrical stimulation of the fastigial nucleus were studied. Effects of conditioning stimulation of the cerebral cortex on those responses were also investigated. Eighteen cats were anaesthetized with a-chloralose (50-80 mg/kg, i.v.), immobilized with gallamine triethiodide and artificially ventilated. Bipolar concentric steel electrodes were placed stereotaxically within the fastigial nucleus contralateral to the recorded thalamus and stimuli were applied with single pulses of 4-20 V intensity and 0.2 msec duration. The position of the electrode tip was histologically verified after the experiment. The exposed bilateral superficial radial nerves were mounted on bipolar silver-wire electrodes in a paraffin pool and were stimulated with single pulses of 0.5-3 V intensity and 0.2 msec duration. Pulses of intensity 2-10 V, 0.5 msec duration and a train of 5 stimuli at 250 Hz were applied to a pair of silverball electrodes laid on the anterior sigmoid gyrus ipsilateral to the thalamus recorded. The intralaminar thalamic neurones were located stereotaxically through the intact cortex and records were made extraceltularly by means of glass micropipettes containing 3 M KC! of 6-20 M ~ impedance. Intralaminar neurones responded to stimulation of each o f 4 extremities in a convergent manner with rather long response latencies around 25 msec (Fig. IA and
173
i,=,....a
0
JJJ
jl
i
i
_
~lllWliilllllltl
d Fig. 1. Responses of an intralaminar thalamic neurone to ipsilateral (A) and contralateral (B) superficial radial nerve stimulation with a typical response pattern of convergence. C: response of the same neurone as (A) and (B) to the contralateral fastigial stimulation. D: short and long latency responses to fastigial stimulation. E: spontaneous unit discharge of a thalamic neurone inhibited by a single shock to the fastigial nucleus. Calibrations: 20 msec for A, B and C; 50 msec for D and E; 5 mV amplitude. B). Moreover those responses were extremely weak to repetitive peripheral stimuli and rarely followed stimulation rates in excess of 8 Hz. These electrophysiological properties of intralaminar neuronal responses were in good accordance with results reported by other investigators7,10-12 and were quite useful in our experiments for the identification of intralaminar neurones responding to fastigial stimulation. A m o n g a total of 153 single units studied, 121 (79~o) units responded to all electrical stimulation of the fastigial nucleus and of the ipsi- and contralateral radial nerve (Fig. 1A-C). Six ( 4 ~ ) units responded only to fastigial stimulation and 26 (17 ~o) units responded only to peripheral stimulation. All the neurones studied were encountered within the stereotaxic limits: A 6.5-8.0, L 1.0-3.0, H + 3 . 0 to --2.0, and according to the histological reconstruction by electrode tracks they were located in nucleus centrum medianum and nucleus parafascicularis. In the present experiments, however, the following studies were made on units which responded both to fastigial and peripheral stimulation. In almost all cases, the spike discharges to fastigial stimulation were identical in shape and amplitude to those obtained following radial nerve stimulation. The response latencies for the first spike in a unit's discharge to fastigial stimulation ranged from 7 to 35 msec and the majority of units responded with latencies from 7 to 15 msec. The mean latency was calculated to be 12.9 msec and, assuming the fastigothalamic pathway to be monosynaptic, the conduction velocity of the fibres should be about 1.46 m/sec. Intralaminar neurones responded to repetitive stimulation of the fastigial nucleus up to 20 Hz without fail. Some neurones showed dual responses to fastigial stimulation at short and long latencies from 100 to 450 msec (Fig. I D). The analogous phenomenon was observed in the case of peripheral stimulation and was in accordance with the results reported by Alb6-Fessard and Kruger 4. Relatively
174
A
v
C
i
1
4.- ~ t r , , , r w ~ t -
]
I
I
Fig. 2. Inhibition and excitation of intralaminar unit responses following cortical stimulation. A unit with a burst of spikes to stimulation of the contralateral fastigial nucleus is shown in A, The response was inhibited by prior stimulation of the cerebral cortex (B). With increased cortical stimulus intensity excitation of the thalamic neurone followed by inhibition of subsequent fastigial response was observed (C), Calibration : 20 msec, 5 mV. few i n t r a l a m i n a r neurones discharged s p o n t a n e o u s l y u n d e r c h l o r a l o s e anaesthesia a n d they were in some cases inhibited for 200-300 msec following single shocks to fastigial nucleus (Fig. t E). The n e u r o n a l mechanism o f the inhibition r e m a i n s to be clarified. A b r i e f volley a p p l i e d to a n t e r i o r s i g m o i d gyrus 50 msec p r i o r to fastigial s t i m u l a t i o n inhibited 109 (90%) i n t r a l a m i n a r unitary responses e v o k e d by fastigial s t i m u l a t i o n (Fig. 2A and B). The r e m a i n i n g 12 units (10%) were not influenced. Effects o f cortical s t i m u l a t i o n on t h a l a m i c responses to fastigial s t i m u l a t i o n were e x a m i n e d at v a r i o u s c o n d i t i o n i n g test intervals. The intervals for onset o f inhibition r a n g e d from 15 to 20 msec and the interval for initial sign o f recovery r a n g e d f r o m 90 to 150 msec as shown in Fig. 3. In o u r e x p e r i m e n t s a c o n d i t i o n i n g test interval o f 50 msec was therefore chosen to e x a m i n e the effects o f cortical stimulation. In m a n y instances cortical s t i m u l a t i o n with stimulus intensities greater t h a n those required for inhibition p r o d u c e d e x c i t a t o r y responses followed by inhibition o f
I00
/
"-i
80 60 40 20
0
20
40
60
80
I00
120
140
160
rllsec
Fig. 3. Time course of cortical inhibition of a thalamic response to fastigial stimulation. Number of spikes as a percentage of t h a t of control response (ordinate) is plotted against interval between conditioning and test stimulation (abscissa). At least 5 conditioning-test interactions were observed at each interval, interspersed with test fastigial stimuli alone.
175 i n t r a l a m i n a r n e u r o n e s r e s p o n d i n g to fastigial s t i m u l a t i o n (Fig. 2C), The responses driven by the cortical volley seemed to be excitatory synaptic ones as they did n o t have fixed response latency, having only 2 or 3 spikes to a t r a i n of 5 stimuli a n d interspike intervals were i n c o n s t a n t in each trial. These excitatory spikes produced by cortical s t i m u l a t i o n were also observed by Albd-Fessard a n d Gillett 2 a n d AlbGFessard et al. 1, who investigated the effects of cortical s t i m u l a t i o n on i n t r a l a m i n a r n e u r o n e s r e s p o n d i n g to peripheral stimulation. The present experiments revealed some electrophysiological properties of the fastigothalamic p a t h w a y ; n o t only afferent i n f o r m a t i o n from each of extremities b u t also cerebellar impulses from the fastigial nucleus 'converge' to the i n t r a l a m i n a r t h a l a m i c neurones. Both excitatory and i n h i b i t o r y influences exerted by cortical s t i m u l a t i o n on i n t r a l a m i n a r n e u r o n e s r e s p o n d i n g to fastigial s t i m u l a t i o n suggest an i n v o l v e m e n t of the cerebral cortex in m o d u l a t i o n of cerebellar i n p u t to the i n t r a l a m i n a r thalamus. We are grateful to Prof. K l a u s R. U n n a for a critical reading of the m a n u s c r i p t , Mr. Masaji T a m a g a w a for electrotechnical assistance in the course of this work a n d Mr. Isao S a k u r a d a for p r e p a r i n g the photographs.
1 ALBI~-FESSARD,D., ]~ESSON,J. M., GUILBAUD,G., AND LEVANTE,A., Cortical control of somatic inflow to medial thalamus. In T. L. FRIGYESI,E. RINVIK AND M. D. YAHR (Eds.), Corticotha/amic Projections and Sensorimotor Activities, Raven Press, New York, 1972, pp. 283-303. 2 ALBI~-FESSARD,D., ET GILLETT,E., Convergences d'affGrences d'origines corticale et pGriphGrique vers le centre mGdian du chat anesthGsi6 ou 6veillG, Electroenceph. clin. Neurophysiol., 13 (1961) 257 269. 3 ALB~,-UESSARD,D., AND KRAUTHAMER,G., Inhibition of units of the non-specific afferent system by stimulation of the basal ganglia, J. Physiol. (Lond.), 175 (1964) 54P-55P. 4 ALB~-FESSARD,D., AND KRUGER, L., Duality of unit discharges from cat centrum medianum in response to natural and electrical stimulation, J. Neurophysiol., 25 (1962) 3-20. 5 CARPENTER,M. B., BARD, D. S., AND ALLING, F. A., Anatomical connections between the fastigial nuclei, the labyrinth and the vestibular nuclei in the cat, J. comp. Neurol., 111 (1959) 1 25. 6 CARPENTER,M. B., BRITTIN,G. M., ArqDPINES, J., Isolated lesions of the fastigial nuclei in the cat, J. comp. Neurol., 109 (1958) 65 89. 7 FELTZ, P., KRAUTHAMER,G., AND ALB~-FESSARO,D., Neurons of the medial diencephalon. 1. Somatosensory responses and caudate inhibition, J. Neurophysiol., 30 (1967) 55-80. 8 KRAUTHAMER,G., AND ALB~-FESSARD,D., Inhibition of nonspecific sensory activities follov,,ing striopallidal and capsular stimulation, J. Neurophysiol., 28 (1965) 100-124. 9 KRUGER,L., AND ALB~-FESSARD,D., Distribution of responses to somatic afferent stimuli in the diencephalon of the cat under chloralose anesthesia, Exp. Neurol., 2 (1960) 442 467. 10 MCKENZIE,J. S., AND GILBERT,D. M., Hippocampal and neostriatal inhibition of medial thalamic unit responses to somatic and brain stem stimulation, Brain Research, 38 (1972) 202-205. 11 MCKENZtE,J. S., GILBERT,D. M., AND ROGERS, D. K., Hippocampal and neostriatal inhibition of extralemniscal thalamic unitary responses in the cat, Brain Research, 27 (1971) 382 385. 12 McKENzlE, J. S., AND ROGERS, D. K., Hippocampal suppression of intralaminar thalamic unit responses in cats and comparison with suppression evoked from the caudate nucleus, Brain Research, 64 (1973) 1-15. 13 PROaST, M., Zur Anatomie und Physiologie des Kleinhirns, Arch. Psychiat. (Nervenkr.), 35 (1902) 692 777. 14 ROGERS, D. K., AND MCKENZIE,J. S., Regional differences within the caudate nucleus for suppression of extralemniscal thalamic units, Brain Research, 56 (1973) 345 349.
