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M4 Muscarinic Recep...
M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia.
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Shen, Weixing (author)
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Plotkin, Joshua L (author)
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- Francardo, Veronica (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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Ko, Wai Kin D (author)
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Xie, Zhong (author)
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Li, Qin (author)
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- Fieblinger, Tim (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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Wess, Jürgen (author)
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Neubig, Richard R (author)
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Lindsley, Craig W (author)
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Conn, P Jeffrey (author)
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Greengard, Paul (author)
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Bezard, Erwan (author)
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- Cenci Nilsson, Angela (author)
- Lund University,Lunds universitet,Basala gangliernas patofysiologi,Forskargrupper vid Lunds universitet,Basal Ganglia Pathophysiology,Lund University Research Groups
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Surmeier, D James (author)
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: Neuron. - : Elsevier BV. - 0896-6273. ; 88:4, s. 762-773
- Related links:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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http://www.cell.com/...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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- art (subject category)
- ref (subject category)
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Neuron
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- By the author/editor
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Shen, Weixing
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Plotkin, Joshua ...
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Francardo, Veron ...
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Ko, Wai Kin D
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Xie, Zhong
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Li, Qin
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show more...
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Fieblinger, Tim
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Wess, Jürgen
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Neubig, Richard ...
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Lindsley, Craig ...
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Conn, P Jeffrey
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Greengard, Paul
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Bezard, Erwan
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Cenci Nilsson, A ...
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Surmeier, D Jame ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Neuron
- By the university
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Lund University