The Role of GABA in Inhibitory Synaptic Inputs on Inhibitory Burst Neurons in the Cat TAKA0 YABE AND NOBUHIKO FURUYA Department of Otolaryngology Teikyo University School of Medicine Kaga 2-11-1, Itabashi-ku Tokyo, Japan In the pontine neural networks that govern vestibular nystagrnus in the cat, inhibitory burst neurons (IBNs) are known to fire in bursts during the quick phase, and to suppress firing of the abducens motoneurons on the contralateral side.' IBNs have direct inhibitory synaptic connections with contralateral abducens motoneurons which terminate their slow-phase activity and play an important role in the generation of fast eye movements. The inhibitory input of IBNs consists of bilateral monosynaptic axonal connections with pause neurons (PNs), and their excitatory input consists of ipsilateral projections from excitatory burst neurons. As mentioned above, the circuitry and functional role of premotor burst neurons have been investigated in detail, but there have been few systematic studes of potential neurotransmitters of these nystagrnus-related neuron^^.^ and the neurotransmitter controlling their burst activity has not yet been identified. The present experiments were designed to identify the neurotransmitter that controls the burst firing activity of IBNs. The experiments were performed on 30 adult cats. Inhibitory burst neuron activity was recorded extracellularly, and various chemicals were applied to the IBNs iontophoretically through seven-barrel micropipettes. Iontophoretic application of y-aminobutyric acid (GABA) strongly suppressed IBN activity and eliminated the burst pattern. In order to examine GABA receptor subtypes, GABAA-receptor agonist and antagonist were administered. Iontophoretic application of muscimol (a GABAA-receptor agonist) showed the same suppression of IBN activity as GABA application. Bicuculline (a GABAA-receptor antagonist) increased the firing of IBNs and suppressed the inhibitory effect of GABA when applied simultaneously. Neither glycine nor serotonin, other inhibitory transmitter candidates in the central nervous Results of Iontophoretic Administration of GABA, the GABA Agonist, the GABA Antagonist, Glycine, and Serotonin"

TABLEI.

Drug GABA Muscimol Bicuculline Glycine Serotonin

Inhibition 39 11 0 1 3

+

Inhibition 2 3 18 8 13

-

Total 41 14 18 9 16

Inhibition +: inhibition of IBN activity. Inhibition -: no effect on IBN activity or suppression of GABA-induced inhibition of IBN. Total: number of neurons iontophoretically treated with the respective chemicals. 964

YABE & FURUYA: ROLE OF GABA

965

system, nor their respective antagonists, strychnine and methysergide, had any effect. 1. SystemiThe results of iontophoretic administrations are summarized in TABLE cally administered picrotoxin (a GABAA-receptorantagonist) prevented the GABAinduced suppression of IBNs. These results suggested that IBNs possess GABAA receptor and are controlled by GABAergic afferent neurons and CI- channels. Based on recent physiological studies of fiber connections centering on the IBN, it appears that GABAergic afferent neurons may be PNs and that the inhibition of IBNs is caused by PNs. REFERENCES

1. HIKOSAKA, 0. & T. KAWAKAMI.1977. Inhibitory reticular neurons related to the quick phase of vestibular nystagmus-their location and projection. Exp. Brain Res. 27: 377396. 2. FURUYA, N., H. ASHIKAWA, T. YABE & J-I. SUZUKI.1988. The effect of serotonin on the pontine pause neorons in the cat. Adv. Otol. Rhinol. Laryngol. 4 2 224-228. 3. SPENCER, R. F., R. J. WENTHOLD & R. BAKER. 1989. Evidence for glycine as an inhibitory neurotransmitter of vestibular, reticular and prepositus hypoglossi neurons that project to the cat abducens nucleus. J. Neurosci. 9 2718-2736.