Document Detail


Activation of D2-like dopamine receptors reduces synaptic inputs to striatal cholinergic interneurons.
MedLine Citation:
PMID:  10729358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A Pisani; P Bonsi; D Centonze; P Calabresi; G Bernardi
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  20     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-06-02     Completed Date:  2000-06-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  RC69     Citation Subset:  IM    
Affiliation:
Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata, 00133 Rome, Italy. pisani@uniroma2.it
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / metabolism*
Animals
Corpus Striatum / cytology,  physiology*
Electrophysiology
Excitatory Postsynaptic Potentials / physiology
Interneurons / metabolism,  physiology*
Male
Membrane Potentials / physiology
Rats
Rats, Wistar
Receptors, Dopamine D2 / physiology*
Receptors, GABA-A / physiology
Receptors, Glutamate / physiology
Receptors, Muscarinic / physiology
Synapses / physiology*
Synaptic Transmission / physiology
Chemical
Reg. No./Substance:
0/Receptors, Dopamine D2; 0/Receptors, GABA-A; 0/Receptors, Glutamate; 0/Receptors, Muscarinic; 51-84-3/Acetylcholine

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