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 glutamatergic inputs. By means of an electrophysiological approach from corticostriatal slices, we isolated three distinct synaptic inputs to cholinergic interneurons: glutamate-mediated EPSPs, GABAA-mediated potentials, and Acetylcholine (ACh)-mediated IPSPs. We therefore explored 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 GABAA and cholinergic synaptic potentials. These effects of quinpirole were mimicked by omega-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-like-mediated postsynaptic mechanism or a presynaptic inhibition of the GABAergic and cholinergic inhibitory synaptic potentials.
Pisani
A
A
Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata, 00133 Rome, Italy. pisani@uniroma2.it
Bonsi
P
P
Centonze
D
D
Calabresi
P
P
Bernardi
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D011976:Receptors, Muscarinic; D000109:Acetylcholine