ParkinsonFranceV1, Hal, Corpus, bibRecord, 000649

M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia.

Identifieur interne : 000649 ( Hal/Corpus ); précédent : 000648; suivant : 000650

M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia.

Auteurs : Weixing Shen ; Joshua L. Plotkin ; Veronica Francardo ; Wai Kin D. Ko ; Zhong Xie ; Qin Li ; Tim Fieblinger ; Jürgen Wess ; Richard R. Neubig ; Craig W. Lindsley ; P Jeffrey Conn ; Paul Greengard ; Erwan Bezard ; M Angela Cenci ; D James Surmeier

Source :

Neuron [ 0896-6273 ] ; 2015-11-18.

RBID : Hal:hal-01286289

Abstract

A balanced interaction between dopaminergic and cholinergic signaling in the striatum is critical to goal-directed behavior. But how this interaction modulates corticostriatal synaptic plasticity underlying learned actions remains unclear--particularly in direct-pathway spiny projection neurons (dSPNs). Our studies show that in dSPNs, endogenous cholinergic signaling through M4 muscarinic receptors (M4Rs) promoted long-term depression of corticostriatal glutamatergic synapses, by suppressing regulator of G protein signaling type 4 (RGS4) activity, and blocked D1 dopamine receptor dependent long-term potentiation (LTP). Furthermore, in a mouse model of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in Parkinson's disease (PD), boosting M4R signaling with positive allosteric modulator (PAM) blocked aberrant LTP in dSPNs, enabled LTP reversal, and attenuated dyskinetic behaviors. An M4R PAM also was effective in a primate LID model. Taken together, these studies identify an important signaling pathway controlling striatal synaptic plasticity and point to a novel pharmacological strategy for alleviating LID in PD patients.

Url:

https://hal.archives-ouvertes.fr/hal-01286289

DOI: 10.1016/j.neuron.

Links to Exploration step

Hal:hal-01286289

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<author><name sortKey="Cenci, M Angela" sort="Cenci, M Angela" uniqKey="Cenci M" first="M Angela" last="Cenci">M Angela Cenci</name>
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<author><name sortKey="Surmeier, D James" sort="Surmeier, D James" uniqKey="Surmeier D" first="D James" last="Surmeier">D James Surmeier</name>
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<idno type="DOI">10.1016/j.neuron.</idno>
<series><title level="j">Neuron</title>
<idno type="ISSN">0896-6273</idno>
<imprint><date type="datePub">2015-11-18</date>
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<front><div type="abstract" xml:lang="en">A balanced interaction between dopaminergic and cholinergic signaling in the striatum is critical to goal-directed behavior. But how this interaction modulates corticostriatal synaptic plasticity underlying learned actions remains unclear--particularly in direct-pathway spiny projection neurons (dSPNs). Our studies show that in dSPNs, endogenous cholinergic signaling through M4 muscarinic receptors (M4Rs) promoted long-term depression of corticostriatal glutamatergic synapses, by suppressing regulator of G protein signaling type 4 (RGS4) activity, and blocked D1 dopamine receptor dependent long-term potentiation (LTP). Furthermore, in a mouse model of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in Parkinson's disease (PD), boosting M4R signaling with positive allosteric modulator (PAM) blocked aberrant LTP in dSPNs, enabled LTP reversal, and attenuated dyskinetic behaviors. An M4R PAM also was effective in a primate LID model. Taken together, these studies identify an important signaling pathway controlling striatal synaptic plasticity and point to a novel pharmacological strategy for alleviating LID in PD patients.</div>
</front>
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            <author role="aut">              <persName>                <forename type="first">Joshua L</forename>
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              <date type="whenProduced">2015-11-18</date>
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              <monogr>                <idno type="halJournalId" status="VALID">17392</idno>
                <idno type="issn">0896-6273</idno>
                <title level="j">Neuron</title>
                <imprint>                  <publisher>Elsevier</publisher>
                  <biblScope unit="volume">88</biblScope>
                  <biblScope unit="issue">4</biblScope>
                  <biblScope unit="pp">762-73</biblScope>
                  <date type="datePub">2015-11-18</date>
                </imprint>
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              <idno type="doi">10.1016/j.neuron.</idno>
              <idno type="pubmed">26590347</idno>
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            <abstract xml:lang="en">A balanced interaction between dopaminergic and cholinergic signaling in the striatum is critical to goal-directed behavior. But how this interaction modulates corticostriatal synaptic plasticity underlying learned actions remains unclear--particularly in direct-pathway spiny projection neurons (dSPNs). Our studies show that in dSPNs, endogenous cholinergic signaling through M4 muscarinic receptors (M4Rs) promoted long-term depression of corticostriatal glutamatergic synapses, by suppressing regulator of G protein signaling type 4 (RGS4) activity, and blocked D1 dopamine receptor dependent long-term potentiation (LTP). Furthermore, in a mouse model of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in Parkinson's disease (PD), boosting M4R signaling with positive allosteric modulator (PAM) blocked aberrant LTP in dSPNs, enabled LTP reversal, and attenuated dyskinetic behaviors. An M4R PAM also was effective in a primate LID model. Taken together, these studies identify an important signaling pathway controlling striatal synaptic plasticity and point to a novel pharmacological strategy for alleviating LID in PD patients.</abstract>
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	La maladie de Parkinson en France (serveur d'exploration)
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La maladie de Parkinson en France (serveur d'exploration)

M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia.

M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia.

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