Dopamine (DA) plays a crucial role in the modulation of striatal function. Striatal cholinergic interneurons represent an important synaptic target of dopaminergic fibers arising from the substantia nigra and cortical glutamatergic inputs. By means of an electrophysiological approach from corticostriatal slices, we isolated three distinct synaptic inputs to cholinergic interneurons: glutamate-mediated EPSPs, GABA A -mediated potentials, and Acetylcholine (ACh)-mediated IPSPs. We therefore

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... ed whether DA controls the striatal cholinergic activity through the modulation of these synaptic potentials. We found that SKF38393, a D1-like receptor agonist, induced a membrane depolarization (also see Aosaki et al., 1998) but had no effects on glutamatergic, GABAergic, and cholinergic synaptic potentials. Conversely, D2-like DA receptor activation by quinpirole inhibited both GABA A and cholinergic synaptic poten-tials. These effects of quinpirole were mimicked by -conotoxin GVIA, blocker of N-type calcium channels. The lack of effect both on the intrinsic membrane properties and on exogenously applied GABA and ACh by quinpirole supports a presynaptic site of action for the D2-like receptor-mediated inhibition. Moreover, the quinpirole-induced decrease in amplitude was accompanied by an increase in paired pulse facilitation ratio (EPSP2/ EPSP1), an index of a decrease in transmitter release. Our findings demonstrate that DA modulates the excitability of cholinergic interneurons through either an excitatory D1-likemediated postsynaptic mechanism or a presynaptic inhibition of the GABAergic and cholinergic inhibitory synaptic potentials. Cholinergic interneurons are relatively large (20 -50 m) aspiny neurons accounting for Ͻ5% of the total neuronal population of the striatum and express both D1-and D2-like dopamine (DA) receptors (Le Moine et al., 1990 . Recently, Yan and coworkers (1997) have shown that the large majority (90%) of these interneurons express D5 receptor mRNA rather than D1; likewise, D3 and D4 mRNAs were undetectable, whereas all the interneurons expressed D2 mRNA. Two main physiological effects of DA on striatal cholinergic interneurons are attributed to the stimulation of postsynaptic D1-like DA receptors: depolarization and inward current with an increase, a decrease, or no change in membrane conductance (Aosaki et al.