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2011年05月26日

Striatal GABA-A control on local and cortical activity in monkeys

日 時 2011年05月26日(木) 15:00 より 17:00 まで
講演者 Olivier Darbin
講演者所属 Department of Neurology, University of South Alabama College of Medicine, Mobile, AL 36608, USA
お問い合わせ先 南部 篤
要旨

The striatum is the major input nucleus of the basal ganglia and receives glutamatergic inputs from cortex and thalamus. This structure exhibits a complex gabaergic circuitry composed by different subpopulations of interneurons and collaterals arising from the output neurons of the striatum. Despite an extensive histological and neurochemical characterization of this nucleus, its functional contribution on the activities of the cortico-cortical loops remains unclear. To elucidate the role of ambient striatal γ-aminobutyric acid (GABA) in the regulation of neuronal activity in the basal ganglia-thalamocortical circuits, we studied the effects of blocking striatal GABAA receptors on the electrical activities of single striatal neurons, on local field potentials (LFPs) in the striatum, and on motor cortical electroencephalograms (EEGs) in two monkeys.

Striatal LFPs were recorded with a device that allowed us to simultaneously record field potentials and apply drugs by reverse microdialysis at the same site. Administration of the GABAA-receptor antagonist gabazine induced large-amplitude LFP fluctuations at the infusion site These events were prevented by cotreatment with a GABAA-receptor agonist (muscimol) or a combination of ionotropic glutamate receptor antagonists (CNQX and MK-801). Gabazine also increased the firing of single neurons recorded close to the injection site, but in most cases there was no correlation between single-neuron activity and the concomitantly recorded LFP signals from the same striatal region. In contrast, intrastriatal application of gabazine increased the correlation between striatal LFPs and EEG, and resulted in the appearance of recurrent EEG events that were temporally related to the striatal LFP events.

These data provide electrophysiological evidence that a GABAergic "tone" in the monkey striatum controls the spontaneous activity of striatal neurons, as well as the level of striatal and cortical synchrony. Therefore, the modulation of the striatal GABAergic neurotransmission can be considered as a putative pharmacological target to control abnormal cortico-cortical synchronizations that occur in movement disorders or epilepsy.

 Olivier Darbin博士は、外国人研究員として4月から3ヶ月間の予定で、生体 システム研究部門に滞在しています。これまでの博士の研究について、とくに霊 長類の大脳基底核におけるGABA性コントロールについてのセミナーをお願いしま した。是非、御来聴下さい。