Role of the basal ganglia in manifestation of rhythmical jaw movement in rats

Brain Research, 535 (1990) 335-338 Elsevier

335

BRES 24424

Role of the basal ganglia in manifestation of rhythmical jaw movement in rats Satoshi Nakamura, Shinichi Muramatsu and Mitsuo Yoshida Department of Neurology, Jichi Medical School Tochigiken (Japan)

(Accepted 28 August 1990) Key words: Striatum; Caudate-putamen; Basal ganglia; Picrotoxin; Rhythmical jaw movement; Neuronal mechanism; Rat; Mastication

Microinjection of picrotoxin (PTX), a selective GABA antagonist, into the rostral part of the head of the caudate-putamen complex (CPC) produced rhythmical potentials of 3-11 Hz there that lasted for about 5-15 s in the rat. Rhythmical jaw movements (RJM) were observed to be associated with these rhythmical potentials. Since the potentials were still observed even after the CPC had been isolated, they were thought to be generated intrinsically by the CPC itself. Increased and grouped neuronal discharges of the CPC were recorded in association with the rhythmical potentials. Periodic or prolonged inhibition of neurons of the pars reticulata of the substantia nigra were also recorded in association with the rhythmical potentials in the CPC. We therefore propose that the basal ganglia are involved directly in the manifestation of RJM in the rat. Electrical stimulation of the cerebral cortex (CX) is known to produce rhythmical jaw movements (RJM) 5'1°. For the RJM, the involvement of 'central pattern generator' (CPG) within the lower brainstem has also been pointed out 2'6'9'12. On the other hand, the basal ganglia may also play an important role in the manifestation of RJM, since (1) systemic administration of a dopamine agonist resulted in production of RJM4; (2) destruction of the superior colliculus, a target structure of the major output system of the basal ganglia, inhibited manifestation of RJM1; (3) local administration of an antagonist of ~,-aminobutyric acid ( G A B A ) into the superior colliculus produced stereotyped oral behavior 16. In order to clarify the role of the basal ganglia in the manifestation of RJM, we have manipulated the caudate-putamen complex (CPC) of the rat by microinjection of picrotoxin (PTX). Fifty Wistar albino rats, of either sex and weighing 280-300 g, were used. Anesthesia was maintained by subcutaneous injection of pentobarbital sodium (10-15 mg/kg). Ether and local injections of procaine were also used. The rat's head was fixed in a stereotaxic apparatus. The left cranium was removed and the left cerebral hemisphere was exposed. The dura was punctured by a 21-gauge needle, and the Hamilton syringe (o.d.: 350 pm) was inserted vertically into the left CPC through the hole in the dura. Stereotaxic coordinates 14 were anterior 2.0 mm and lateral 2.5 mm from the bregma and the depths of either 5 or 3 m m from the surface of CX or the corpus callosum (CC), respectively. PTX (Sigma Chem-

ical Co., 1 pg/1/zl saline) was injected into the CPC at a rate of 0.5/~l/min. The extent of diffusion of PTX within the rostral part of the head of the CPC was determined by incorporation of a saturating amount of Fast green FCF dye into the PTX solution and was found to be less than 1 mm in diameter, for the extent of PTX diffusion corresponds to that of Fast green FCF is. Elgiloy wires of 0.45 mm diameter, electrolytically sharpened and insulated by glass coating except for the tip (resistance, 0.8-1.6 M~2), were used for recording of field potentials as well as extracellular unitary spikes of the rostral part of the head of the CPC or the SNr. The recording sites were verified histologically. An Ag-AgCI electrode was placed on the right ear bar as an indifferent electrode. Electromyograms (EMG's) were recorded differentially between 2 needles inserted into the right masseter muscle. The signals were displayed on a 4-channel oscilloscope (VC-10, Nihon Kohden, Tokyo) through a 4-channel conventional preamplifier and on an E E G machine. For identification of recording areas, negative DC current of 3 V was passed for 20 s. The brain was fixed in 10% formal saline, and frontal sections of 100pm thickness were cut and stained by the Kltiver-Barrera method. Microinjection of PTX into the CPC often produced rhythmical potentials within the CPC. Nine min after PTX injection, rhythmical potentials appeared within the CPC as shown in Fig. 1A. Each of these repetitive potentials consisted of an initial sharp spike and a

Correspondence: M. Yoshida, Department of Neurology, Jichi Medical School, Tochigiken, Japan 329-04.

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potentials within the CPC (upper row) associated with EMG activity of the right masseter muscle (lower row) occurred with one-to-one correspondence to the rhythmical potentials. B: frequency of the EMG activity was lower than that of the rhythmical potentials in the CPC. C: rhythmical potentials in the CPC. The cerebral cortex was ablated (dotted area in the right diagram) and CPC was isolated from the thalamus and the substantia nigra by movement of a spatula (S in the left diagram). Low pass filter: 0.1 Hz for CPC and 0.1 kHz for EMG's. CPC, caudate-putamen complex. Br, bregma.Cx, cerebral cortex. CC, corpus callosum. Acc, nucleus accumbens. Diagram on the right, frontal section at the level of a horizontal line in the left diagram. Oblique arrow, area where PTX was injected.

succeeding slow negative component. The frequency ranged widely from 3 to 11 Hz, and the whole duration of the rhythmical potentials was usually between 5 and 15 s, with the shortest being less than 1 s and the longest, more than 30 s. Rhythmical opening and closing of the jaw appeared in association with the rhythmical potentials within the CPC. As seen in Fig. 1A, EMG activity of the masseter muscle corresponding to rhythmical A

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Fig. 2. Changes in the unitary spike activity of CPC and SNr in response to rhythmical potentials of CPC. A: 1st and 3rd rows, field potentials of the rostral part of the head of the CPC. 2nd and 4th rows, unitary spikes of CPC neurons. B and C: upper rows, field potentials of CPC. Lower rows, unitary spikes of 2 different SNr neurons.

potentials of the CPC in a one-to-one manner was observed in 2/3 of about 500 rhythmical potential sequences recorded in the CPC. On the other hand, rhythmical E M G activity not in one-to-one correspondence with the rhythmical potentials was observed in about 10% of the recorded rhythmical potentials of the CPC (Fig. 1B). There was a tendency for the latter to occur when the frequency of the rhythmical CPC potentials was rather high, such as greater than 9 Hz. In a few instances, rhythmical potentials alone occurred within the CPC, unaccompanied by RJM. Even when the frontal cortex including the masticatory area is ablated by suction (n = 5), rhythmical potentials still appeared in the CPC and were accompanied by RJM. Furthermore, we tried to isolate the CPC from its major inputs by ablating the cerebral cortex as extensively as possible and inputs from the substantia nigra (pars compacta) as well as the thalamus by using a spatula (n = 5, see inserted diagrams of Fig. 1). Even so, the rhythmical potentials were still recorded within the CPC, as shown in Fig. 1C. Extracellular unitary spikes were recorded from the CPC and from the SNr where the efferent fibers from the CPC terminate. As shown in Fig. 2A, the firing rate of extracellularly recorded spikes of the CPC increased intensively as soon as the rhythmical potential sequence started. Furthermore a tendency of grouping of dis-

337 charges in correspondence with each rhythmical potential was also observed. All 19 CPC neurons recorded showed the same tendency as that shown in Fig. 2A. Sixty-one out of 65 SNr neurons recorded exhibited inhibition when rhythmical potential sequences occurred in the CPC. As shown in Fig. 2B, the inhibition tended to occur synchronously with each potential of the rhythmical potentials of the CPC; and such inhibition was noted in 42 out of the 65 SNr neurons. On the other hand, in 15 out of them long-lasting inhibition was observed for the whole phase of the rhythmical potential sequence, as shown in Fig. 2C. In 4 of the 65 SNr neurons, no inhibition was observed. On the other hand, grouped discharges of small amplitude were observed to be in synchrony with each wave of the rhythmical potentials in all records, as seen in Fig. 2B and C. Local administration of PTX, a selective G A B A antagonist, can result in blockage of G A B A e r g i c inhibitory effects on the striatal neurons (see also below) and thus produce activation of the striatal efferent fibers. The fact that rhythmical potentials could also be observed after isolation of the CPC from its major afferents indicates that the rhythmical potentials could be produced by an intrinsic mechanism of the CPC. Major efferent fibers of the CPC are G A B A e r g i c 3"15 and inhibitory in nature 19. These efferent neurons also make abundant G A B A e r g i c inhibitory synapses with axon collaterals 3'13 as well as with G A B A e r g i c interneurons 7. Blockage of the GABA-synapses by PTX could result in an increased rate of firing of the CPC neurons 8. For the formation of the rhythm, however, involvement of an inhibitory process might also be essential. As a source of this inhibition, striatal areas where the antagonizing effect of PTX has not yet been reached may exert an inhibitory effect on the area where it has already been reached. A n alternative source of the inhibition would be

summation of afterhyperpolarizations due to the excessive firing of the neurons. The striatum exerts an inhibitory effect on the SNr 15' 19, and the SNr in turn exerts an inhibition of the superior colliculus 11, the thalamus 17, and also the pedunculopontine nucleus tl. It is, therefore, reasonable that most of the SNr neurons recorded were inhibited in association with the rhythmical potential formation of the CPC, which was accompanied by increased firing of CPC neurons. The inhibition of SNr neurons in turn disinhibits activities of neurons of the superior colliculus or other structures, since the SNr per se is also inhibitory in nature. The question whether all R J M are due to this dis-inhibitory mechanism or not should further be clarified, since about 25% of the SNr neurons recorded showed prolonged inhibition for the whole course of rhythmical potentials of the CPC although more than half of them did show rhythmical inhibition. A structure such as the CPG of the brainstem may also be active during the period of long-lasting inhibition of SNr neurons. In our experiments the frequency of R J M did not correspond with that of rhythmical potentials of the CPC in a one-to-one manner when the frequency of CPC potentials was high. In this kind of situation the frequency of RJM could possibly be regulated also by the C P G of the brainstem. Rhythmical grouped discharges with small amplitude never grew to the amplitude of those of SNr neurons. We think that the grouped discharge was due to electrotonic reflection of the excited neurons outside the SNr (see ref. 8). In conclusion the basal ganglia are thought to be closely linked to masticatory movements.

1 Chandler, S.H. and Goldberg, L.J., Differentiation of neural pathways mediating cortically induced dopaminergic activation of the central pattern generator (CPG) for rhythmical jaw movements in the anesthetized guinea pig, Brain Research, 323 (1984) 297-301. 2 Chandler, S.H. and Tal, M., The effects of brain stem transections on the neuronal networks responsible for rhythmical jaw muscle activity in the guinea pig, J. Neurosci., 6 (1986) 1831-1842. 3 Delgado, J.M.R., Inhibitory functions of the neostriatum. In I. Divac and R.G.E. Oberg (Eds.), The Neostriatum, Pergamon, Oxford, 1979, pp. 241-261. 4 Di Chiara, G. and Gessa, G.L., Pharmacology and neurochemistry of apomorphine. In S. Garattini, A. Goldin, E Hawking and I.J. Kopin (Eds.), Advances in Pharmacology and Chemotherapy, Vol. 15, Academic Press, New York, 1981, pp. 87-160. 5 Luschei, E.S. and Goldberg, L.J., Neural mechanisms of mandibular control. In J.M. Brookhart, V.B. Mountcastle, V.B. Brooks and S.R. Geiger (Eds.), Handbook of Physiology, Vol. 2, Motor Control, Part 2, American Physiological Society, Bethesda, MD, 1981, pp. 1237-1274.

6 Marini, G. and Sotgiu, M.L., Single unit activity in lateral reticular nucleus during cortically evoked masticatory movements in rabbits, Brain Research, 337 (1985) 287-292. 7 McGeer, P.L. and McGeer, E.G., Evidence for glutamic acid decarboxylase-containing interneurons in the neostriatum, Brain Research, 91 (1975) 331-335. 8 Muramatsu, S., Yoshida, M. and Nakamura, S., Electrophysiological study of dyskinesia produced by microinjection of picrotoxin into the striatum of the rat, Neurosci. Res., 7 (1990) 369-380. 9 Nakamura, Y., Enomoto, S. and Katoh, M., The role of medial bulbar reticular neurons in the orbital cortically induced masticatory rhythm in cats, Brain Research, 202 (1980) 207-212. 10 Nakamura, Y., Takatori, Y., Kubo, S., Nozaki, S. and Enomoto, S., Masticatory rhythm formation-facts and a hypothesis. In N. Tsukahara, K. Kubota and K. Yagi (Eds.), Integrative Control Functions of the Brain, Vol. 2, Kodansha Scientific, Tokyo, 1979, pp. 321-331. 11 Niijima, K. and Yoshida, M., Electrophysiological evidence for branching nigral projections to pontine reticular formation, superior colliculus and thalamus, Brain Research, 239 (1982)

This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, and Culture of Japan.

338 279-282. 12 Nozaki, S., Iriki, A. and Nakamura, Y., Role of corticobulbar projection neurons in cortically induced rhythmical masticatory jaw-opening movement in the guinea pig, J. Neurophysiol., 55 (1986) 826-845. 13 Park, M.R., Lighthall, J.W. and Kitai, S.T., Recurrent inhibition in the rat neostriatum, Brain Research, 194 (1980) 359-369. 14 Pellegrino, L.J., Pellegrino, A.S. and Cushman, A.J. (Eds.), A Stereotaxic Atlas of the Rat Brain, 2nd Edn., Plenum, New York, 1979. 15 Precht, W. and Yoshida, M., Blockage of caudate-evoked inhibition of neurons in the substantia nigra by picrotoxin, Brain Research, 32 (1971) 229-233. 16 Redgrave, P., Dean, P., Souki, W. and Lewis, G., Gnawing and

changes in reactivity produced by microinjections of picrotoxin into the superior colliculus of rats, Psychopharmacology, 75 (1981) 198-203. 17 Ueki, A., The mode of nigro-thalamic transmission investigated with intracellular recording in the cat, Exp. Brain Res., 49 (1983) 116-124. 18 Yoshida, M., Nagatsuka, Y., Muramatsu, S. and Niijima, K., Differential roles of the caudate nucleus and putamen in motor behavior of the cat as investigated by local injection of GABA antagonist, Neurosci. Res., in press. 19 Yoshida, M. and Precht, W., Monosynaptic inhibition of neurons of the substantia nigra by caudate-nigral fibers, Brain Research, 32 (1971) 225-228.