作者
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
发表日期
2015/11/18
期刊
Neuron
卷号
88
期号
4
页码范围
762-773
出版商
Elsevier
简介
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 …
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W Shen, JL Plotkin, V Francardo, WKD Ko, Z Xie, Q Li… - Neuron, 2015