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., Bonsi, P., Centonze, D., Calabresi, P., Bernardi, G. (2000). Activation of D2-like dopamine receptors reduces synaptic inputs to striatal cholinergic interneurons. THE JOURNAL OF NEUROSCIENCE, 20(7), RC69.

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

PISANI, ANTONIO;CENTONZE, DIEGO;CALABRESI, PAOLO;BERNARDI, GIORGIO
2000-04-01

Abstract

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.
1-apr-2000
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
Acetylcholine; Electrophysiology; Corpus Striatum; Male; Synapses; Receptors, Dopamine D2; Rats, Wistar; Receptors, Muscarinic; Rats; Animals; Interneurons; Receptors, Glutamate; Membrane Potentials; Excitatory Postsynaptic Potentials; Receptors, GABA-A; Synaptic Transmission
Pisani, A., Bonsi, P., Centonze, D., Calabresi, P., Bernardi, G. (2000). Activation of D2-like dopamine receptors reduces synaptic inputs to striatal cholinergic interneurons. THE JOURNAL OF NEUROSCIENCE, 20(7), RC69.
Pisani, A; Bonsi, P; Centonze, D; Calabresi, P; Bernardi, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/51511
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