Differential contribution of dopamine D2S and D2L receptors in the modulation of glutamate and GABA transmission in the striatum
Identifieur interne : 000686 ( PascalFrancis/Curation ); précédent : 000685; suivant : 000687Differential contribution of dopamine D2S and D2L receptors in the modulation of glutamate and GABA transmission in the striatum
Auteurs : D. Centonze [Italie] ; P. Gubellini [Italie, France] ; A. Usiello [France] ; S. Rossi [Italie] ; A. Tscherter [Italie] ; E. Bracci [Italie, Royaume-Uni] ; E. Erbs [France] ; N. Tognazzi [France] ; G. Bernardi [Italie] ; A. Pisani [Italie] ; P. Calabresi [Italie] ; E. Borrelli [France]Source :
- Neuroscience [ 0306-4522 ] ; 2004.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Animal transgénique.
English descriptors
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Abstract
Compelling evidence indicates that the long (D2L) and the short (D2S) isoform of dopamine (DA) D2 receptors serve distinct physiological functions in vivo. To address the involvement of these isoforms in the control of synaptic transmission in the striatum, we measured the sensitivity to D2 receptor stimulation of glutamate- and GABA-mediated currents recorded from striatal neurons of three mutant mice, in which the expression of D2L and D2S receptors was either ablated or variably altered. Our data indicate that both isoforms participate in the presynaptic inhibition of GABA transmission in the striatum, while the D2-receptor-dependent modulation of glutamate release preferentially involves the D2S receptor. Accordingly, the inhibitory effects of the DA D2 receptor agonist quinpirole (10 μM) on GABAA-mediated spontaneous inhibitory postsynaptic currents (IPSCs) correlate with the total number of D2 receptor sites in the striatum, irrespective of the specific receptor isoform expressed. In contrast, glutamate-mediated spontaneous excitatory postsynaptic currents (EPSCs) were significantly inhibited by quinpirole only when the total number of D2 receptor sites, normally composed by both D2L and D2S receptors in a ratio favoring the D2L isoform, was modified to express only the D2S isoform at higher than normal levels. Understanding the physiological roles of DA D2 receptors in the striatum is essential for the treatment of several neuropsychiatric conditions, such as Parkinson's disease, Tourette's syndrome, schizophrenia, and drug addiction.
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Calabresi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Borrelli, E" sort="Borrelli, E" uniqKey="Borrelli E" first="E." last="Borrelli">E. Borrelli</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Medicale-ULP, Rue L. Fries, BP10142</s1><s2>67404 Illkirch</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">04-0596648</idno><date when="2004">2004</date><idno type="stanalyst">PASCAL 04-0596648 INIST</idno><idno type="RBID">Pascal:04-0596648</idno><idno type="wicri:Area/PascalFrancis/Corpus">000D48</idno><idno type="wicri:Area/PascalFrancis/Curation">000686</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Differential contribution of dopamine D2S and D2L receptors in the modulation of glutamate and GABA transmission in the striatum</title><author><name sortKey="Centonze, D" sort="Centonze, D" uniqKey="Centonze D" first="D." last="Centonze">D. Centonze</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Gubellini, P" sort="Gubellini, P" uniqKey="Gubellini P" first="P." last="Gubellini">P. Gubellini</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Interactions Cellulaires, Neurodégénérescence et Neuroplasticité (IC2N-UMR6186), CNRS-Université de la Méditerranée</s1><s2>Marseille</s2><s3>FRA</s3><sZ>2 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Usiello, A" sort="Usiello, A" uniqKey="Usiello A" first="A." last="Usiello">A. Usiello</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Medicale-ULP, Rue L. Fries, BP10142</s1><s2>67404 Illkirch</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Rossi, S" sort="Rossi, S" uniqKey="Rossi S" first="S." last="Rossi">S. Rossi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Tscherter, A" sort="Tscherter, A" uniqKey="Tscherter A" first="A." last="Tscherter">A. Tscherter</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Bracci, E" sort="Bracci, E" uniqKey="Bracci E" first="E." last="Bracci">E. Bracci</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Optometry and Neuroscience, UMIST</s1><s2>Manchester M60 1QD</s2><s3>GBR</s3><sZ>6 aut.</sZ></inist:fA14><country>Royaume-Uni</country></affiliation></author><author><name sortKey="Erbs, E" sort="Erbs, E" uniqKey="Erbs E" first="E." last="Erbs">E. Erbs</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Medicale-ULP, Rue L. Fries, BP10142</s1><s2>67404 Illkirch</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Tognazzi, N" sort="Tognazzi, N" uniqKey="Tognazzi N" first="N." last="Tognazzi">N. Tognazzi</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Medicale-ULP, Rue L. Fries, BP10142</s1><s2>67404 Illkirch</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Bernardi, G" sort="Bernardi, G" uniqKey="Bernardi G" first="G." last="Bernardi">G. Bernardi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Pisani, A" sort="Pisani, A" uniqKey="Pisani A" first="A." last="Pisani">A. Pisani</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Calabresi, P" sort="Calabresi, P" uniqKey="Calabresi P" first="P." last="Calabresi">P. Calabresi</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Borrelli, E" sort="Borrelli, E" uniqKey="Borrelli E" first="E." last="Borrelli">E. Borrelli</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Medicale-ULP, Rue L. Fries, BP10142</s1><s2>67404 Illkirch</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country></affiliation></author></analytic><series><title level="j" type="main">Neuroscience</title><title level="j" type="abbreviated">Neuroscience</title><idno type="ISSN">0306-4522</idno><imprint><date when="2004">2004</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Neuroscience</title><title level="j" type="abbreviated">Neuroscience</title><idno type="ISSN">0306-4522</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Basal ganglion</term><term>Corpus striatum</term><term>D2L dopamine receptor</term><term>D2S dopamine receptor</term><term>Electrophysiology</term><term>Excitatory postsynaptic current</term><term>GABA</term><term>Glutamatergic transmission</term><term>Inhibitory postsynaptic current</term><term>Synaptic transmission</term><term>Transgenic animal</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Récepteur dopaminergique D2S</term><term>Récepteur dopaminergique D2L</term><term>Transmission glutamatergique</term><term>GABA</term><term>Corps strié</term><term>Noyau gris central</term><term>Electrophysiologie</term><term>Courant postsynaptique excitateur</term><term>Courant postsynaptique inhibiteur</term><term>Transmission synaptique</term><term>Animal transgénique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Animal transgénique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Compelling evidence indicates that the long (D2L) and the short (D2S) isoform of dopamine (DA) D2 receptors serve distinct physiological functions in vivo. To address the involvement of these isoforms in the control of synaptic transmission in the striatum, we measured the sensitivity to D2 receptor stimulation of glutamate- and GABA-mediated currents recorded from striatal neurons of three mutant mice, in which the expression of D2L and D2S receptors was either ablated or variably altered. Our data indicate that both isoforms participate in the presynaptic inhibition of GABA transmission in the striatum, while the D2-receptor-dependent modulation of glutamate release preferentially involves the D2S receptor. Accordingly, the inhibitory effects of the DA D2 receptor agonist quinpirole (10 μM) on GABA<sub>A</sub>-mediated spontaneous inhibitory postsynaptic currents (IPSCs) correlate with the total number of D2 receptor sites in the striatum, irrespective of the specific receptor isoform expressed. In contrast, glutamate-mediated spontaneous excitatory postsynaptic currents (EPSCs) were significantly inhibited by quinpirole only when the total number of D2 receptor sites, normally composed by both D2L and D2S receptors in a ratio favoring the D2L isoform, was modified to express only the D2S isoform at higher than normal levels. Understanding the physiological roles of DA D2 receptors in the striatum is essential for the treatment of several neuropsychiatric conditions, such as Parkinson's disease, Tourette's syndrome, schizophrenia, and drug addiction.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0306-4522</s0></fA01><fA02 i1="01"><s0>NRSCDN</s0></fA02><fA03 i2="1"><s0>Neuroscience</s0></fA03><fA05><s2>129</s2></fA05><fA06><s2>1</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Differential contribution of dopamine D2S and D2L receptors in the modulation of glutamate and GABA transmission in the striatum</s1></fA08><fA11 i1="01" i2="1"><s1>CENTONZE (D.)</s1></fA11><fA11 i1="02" i2="1"><s1>GUBELLINI (P.)</s1></fA11><fA11 i1="03" i2="1"><s1>USIELLO (A.)</s1></fA11><fA11 i1="04" i2="1"><s1>ROSSI (S.)</s1></fA11><fA11 i1="05" i2="1"><s1>TSCHERTER (A.)</s1></fA11><fA11 i1="06" i2="1"><s1>BRACCI (E.)</s1></fA11><fA11 i1="07" i2="1"><s1>ERBS (E.)</s1></fA11><fA11 i1="08" i2="1"><s1>TOGNAZZI (N.)</s1></fA11><fA11 i1="09" i2="1"><s1>BERNARDI (G.)</s1></fA11><fA11 i1="10" i2="1"><s1>PISANI (A.)</s1></fA11><fA11 i1="11" i2="1"><s1>CALABRESI (P.)</s1></fA11><fA11 i1="12" i2="1"><s1>BORRELLI (E.)</s1></fA11><fA14 i1="01"><s1>Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata, " Via Montpellier 1</s1><s2>00133 Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></fA14><fA14 i1="02"><s1>IRCCS Fondazione Santa Lucia, Via Ardeatina 306</s1><s2>00179, Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></fA14><fA14 i1="03"><s1>Interactions Cellulaires, Neurodégénérescence et Neuroplasticité (IC2N-UMR6186), CNRS-Université de la Méditerranée</s1><s2>Marseille</s2><s3>FRA</s3><sZ>2 aut.</sZ></fA14><fA14 i1="04"><s1>Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Medicale-ULP, Rue L. Fries, BP10142</s1><s2>67404 Illkirch</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Optometry and Neuroscience, UMIST</s1><s2>Manchester M60 1QD</s2><s3>GBR</s3><sZ>6 aut.</sZ></fA14><fA20><s1>157-166</s1></fA20><fA21><s1>2004</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>17194</s2><s5>354000120537330160</s5></fA43><fA44><s0>0000</s0><s1>© 2004 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>1 p.1/4</s0></fA45><fA47 i1="01" i2="1"><s0>04-0596648</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Neuroscience</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>Compelling evidence indicates that the long (D2L) and the short (D2S) isoform of dopamine (DA) D2 receptors serve distinct physiological functions in vivo. To address the involvement of these isoforms in the control of synaptic transmission in the striatum, we measured the sensitivity to D2 receptor stimulation of glutamate- and GABA-mediated currents recorded from striatal neurons of three mutant mice, in which the expression of D2L and D2S receptors was either ablated or variably altered. Our data indicate that both isoforms participate in the presynaptic inhibition of GABA transmission in the striatum, while the D2-receptor-dependent modulation of glutamate release preferentially involves the D2S receptor. Accordingly, the inhibitory effects of the DA D2 receptor agonist quinpirole (10 μM) on GABA<sub>A</sub>-mediated spontaneous inhibitory postsynaptic currents (IPSCs) correlate with the total number of D2 receptor sites in the striatum, irrespective of the specific receptor isoform expressed. In contrast, glutamate-mediated spontaneous excitatory postsynaptic currents (EPSCs) were significantly inhibited by quinpirole only when the total number of D2 receptor sites, normally composed by both D2L and D2S receptors in a ratio favoring the D2L isoform, was modified to express only the D2S isoform at higher than normal levels. Understanding the physiological roles of DA D2 receptors in the striatum is essential for the treatment of several neuropsychiatric conditions, such as Parkinson's disease, Tourette's syndrome, schizophrenia, and drug addiction.</s0></fC01><fC02 i1="01" i2="X"><s0>002A25</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Récepteur dopaminergique D2S</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>D2S dopamine receptor</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Receptor dopaminérgico D2S</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Récepteur dopaminergique D2L</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>D2L dopamine receptor</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Receptor dopaminérgico D2L</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Transmission glutamatergique</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Glutamatergic transmission</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Transmision glutamatérgica</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>GABA</s0><s2>NK</s2><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>GABA</s0><s2>NK</s2><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>GABA</s0><s2>NK</s2><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Corps strié</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Corpus striatum</s0><s5>05</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Cuerpo estriado</s0><s5>05</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Noyau gris central</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Basal ganglion</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Núcleo basal</s0><s5>06</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Electrophysiologie</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Electrophysiology</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Electrofisiología</s0><s5>07</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Courant postsynaptique excitateur</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Excitatory postsynaptic current</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Corriente postsináptico excitador</s0><s5>08</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Courant postsynaptique inhibiteur</s0><s5>10</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Inhibitory postsynaptic current</s0><s5>10</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Corriente postsináptico inhibidor</s0><s5>10</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Transmission synaptique</s0><s5>11</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Synaptic transmission</s0><s5>11</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Transmisión sináptica</s0><s5>11</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Animal transgénique</s0><s5>13</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Transgenic animal</s0><s5>13</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Animal transgénico</s0><s5>13</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Neurotransmetteur</s0><s5>20</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Neurotransmitter</s0><s5>20</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Neurotransmisor</s0><s5>20</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Encéphale</s0><s5>21</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Encephalon</s0><s5>21</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Encéfalo</s0><s5>21</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Système nerveux central</s0><s5>22</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Central nervous system</s0><s5>22</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Sistema nervioso central</s0><s5>22</s5></fC07><fN21><s1>341</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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