Effects of striatal GABA(A)-receptor blockade on striatal and cortical activity in monkeys

To elucidate the role of ambient striatal gamma-aminobutyric acid ( GABA) in the regulation of neuronal activity in the basal ganglia - thalamocortical circuits, we studied the effects of blocking striatal GABA(A) 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 GABA(A)-receptor antagonist gabazine ( SR95531, 10 and 500 mu M) induced large- amplitude LFP fluctuations at the infusion site, occurring every 2-5 s for about 2 h after the start of the 20-min drug administration. These events were prevented by cotreatment with a GABA(A)-receptor agonist ( muscimol, 100 mu M) or a combination of ionotropic glutamate receptor antagonists ( CNQX and MK-801, each given at 100 mu M). Gabazine ( 10 mu M) 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 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.