Activation of D2-like dopamine receptors reduces synaptic inputs to striatal cholinergic interneurons

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 glutama tergic inputs. By means of an electrophysiological approach from corticostr iatal slices, we isolated three distinct synaptic inputs to cholinergic int erneurons: glutamate-mediated EPSPs, GABA(A)-mediated potentials, and Acety lcholine (ACh)-mediated IPSPs. We therefore explored whether DA controls th e striatal cholinergic activity through the modulation of these synaptic po tentials. We found that SKF38393, a D1-like receptor agonist, induced a mem brane depolarization (also see Aosaki et al., 1998) but had no effects on g lutamatergic, GABAergic, and cholinergic synaptic potentials. Conversely, D 2-like DA receptor activation by quinpirole inhibited both GABA(A) and chol inergic synaptic potentials. These effects of quinpirole were mimicked by v -conotoxin GVIA, blocker of N-type calcium channels. The lack of effect bot h on the intrinsic membrane properties and on exogenously applied GABA and ACh by quinpirole supports a presynaptic site of action for the D2-like rec eptor-mediated inhibition. Moreover, the quinpirole-induced decrease in amp litude was accompanied by an increase in paired pulse facilitation ratio (E PSP2/EPSP1), an index of a decrease in transmitter release. Our findings de monstrate that DA modulates the excitability of cholinergic interneurons th rough either an excitatory D1-like-mediated postsynaptic mechanism or a pre synaptic inhibition of the GABAergic and cholinergic inhibitory synaptic po tentials.