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

Standard

M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia. / Shen, Weixing; Plotkin, Joshua L; Francardo, Veronica; Ko, Wai Kin D; Xie, Zhong; Li, Qin; Fieblinger, Tim; Wess, Jürgen; Neubig, Richard R; Lindsley, Craig W; Conn, P Jeffrey; Greengard, Paul; Bezard, Erwan; Cenci, M Angela; Surmeier, D James.

in: NEURON, Jahrgang 88, Nr. 4, 18.11.2015, S. 762-73.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Shen, W, Plotkin, JL, Francardo, V, Ko, WKD, Xie, Z, Li, Q, Fieblinger, T, Wess, J, Neubig, RR, Lindsley, CW, Conn, PJ, Greengard, P, Bezard, E, Cenci, MA & Surmeier, DJ 2015, 'M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia', NEURON, Jg. 88, Nr. 4, S. 762-73. https://doi.org/10.1016/j.neuron.2015.10.039

APA

Shen, W., Plotkin, J. L., Francardo, V., Ko, W. K. D., Xie, Z., Li, Q., Fieblinger, T., Wess, J., Neubig, R. R., Lindsley, C. W., Conn, P. J., Greengard, P., Bezard, E., Cenci, M. A., & Surmeier, D. J. (2015). M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia. NEURON, 88(4), 762-73. https://doi.org/10.1016/j.neuron.2015.10.039

Vancouver

Shen W, Plotkin JL, Francardo V, Ko WKD, Xie Z, Li Q et al. M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia. NEURON. 2015 Nov 18;88(4):762-73. https://doi.org/10.1016/j.neuron.2015.10.039

Bibtex

@article{01ff08e5fba54aea923a8fc9d4ab7a63,
title = "M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia",
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.",
keywords = "Allosteric Regulation, Animals, Cerebral Cortex/metabolism, Disease Models, Animal, Dopamine Agents/toxicity, Dyskinesia, Drug-Induced/etiology, Glutamic Acid, Levodopa/toxicity, Long-Term Potentiation/drug effects, Long-Term Synaptic Depression/drug effects, Macaca mulatta, Mice, Mice, Transgenic, Neostriatum/drug effects, Neuronal Plasticity/drug effects, Neurons, Parkinsonian Disorders/drug therapy, RGS Proteins/metabolism, Receptor, Muscarinic M4/metabolism, Signal Transduction",
author = "Weixing Shen and Plotkin, {Joshua L} and Veronica Francardo and Ko, {Wai Kin D} and Zhong Xie and Qin Li and Tim Fieblinger and J{\"u}rgen Wess and Neubig, {Richard R} and Lindsley, {Craig W} and Conn, {P Jeffrey} and Paul Greengard and Erwan Bezard and Cenci, {M Angela} and Surmeier, {D James}",
note = "Copyright {\textcopyright} 2015 Elsevier Inc. All rights reserved.",
year = "2015",
month = nov,
day = "18",
doi = "10.1016/j.neuron.2015.10.039",
language = "English",
volume = "88",
pages = "762--73",
journal = "NEURON",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia

AU - Shen, Weixing

AU - Plotkin, Joshua L

AU - Francardo, Veronica

AU - Ko, Wai Kin D

AU - Xie, Zhong

AU - Li, Qin

AU - Fieblinger, Tim

AU - Wess, Jürgen

AU - Neubig, Richard R

AU - Lindsley, Craig W

AU - Conn, P Jeffrey

AU - Greengard, Paul

AU - Bezard, Erwan

AU - Cenci, M Angela

AU - Surmeier, D James

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/11/18

Y1 - 2015/11/18

N2 - 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.

AB - 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.

KW - Allosteric Regulation

KW - Animals

KW - Cerebral Cortex/metabolism

KW - Disease Models, Animal

KW - Dopamine Agents/toxicity

KW - Dyskinesia, Drug-Induced/etiology

KW - Glutamic Acid

KW - Levodopa/toxicity

KW - Long-Term Potentiation/drug effects

KW - Long-Term Synaptic Depression/drug effects

KW - Macaca mulatta

KW - Mice

KW - Mice, Transgenic

KW - Neostriatum/drug effects

KW - Neuronal Plasticity/drug effects

KW - Neurons

KW - Parkinsonian Disorders/drug therapy

KW - RGS Proteins/metabolism

KW - Receptor, Muscarinic M4/metabolism

KW - Signal Transduction

U2 - 10.1016/j.neuron.2015.10.039

DO - 10.1016/j.neuron.2015.10.039

M3 - SCORING: Journal article

C2 - 26590347

VL - 88

SP - 762

EP - 773

JO - NEURON

JF - NEURON

SN - 0896-6273

IS - 4

ER -