Dual cholinergic control of fast-spiking interneurons in the neostriatum.

GABAergic interneurons appear to play a fundamental role in the functioning of the neostriatum by modulating the spiking of striatal projection neurons with great efficacy. The powerful and strongly divergent output of the GABAergic interneurons neurons suggests that modulation of their activity may be particularly effective at controlling the functioning of the entire neostriatal circuitry. Acetylcholine is one of the main modulators of striatal functioning. The effects of acetylcholine on fast-spiking (FS) GABAergic interneurons were studied with whole-cell recording in an in vitro slice preparation. Acetylcholine exerted two distinct effects on fast-spiking interneurons. Acetylcholine directly depolarized FS interneurons by acting on nondesensitizing soma-dendritic nicotinic receptors. In addition, acetylcholine attenuated the GABAergic inhibition of projection neurons by fast-spiking interneurons through activation of presynaptic muscarinic receptors. It is suggested that the nicotinic excitation of FS interneurons may play an important role in translating the effect of the brief behaviorally contingent cessation of firing of the tonically active cholinergic interneurons to the output neurons of the neostriatum. In contrast, the muscarinic presynaptic inhibitory mechanism may be engaged primarily during longer-lasting elevations of extracellular acetylcholine levels.