Muscarinic M1 Receptor Modulation of Synaptic Plasticity in Nucleus Accumbens of Wild-Type and Fragile X Mice.,ACS Chemical Neuroscience

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Muscarinic M1 Receptor Modulation of Synaptic Plasticity in Nucleus Accumbens of Wild-Type and Fragile X Mice.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2018-03-08 , DOI: 10.1021/acschemneuro.7b00398
Daniela Neuhofer _{1,

2,

3,

4} , Olivier Lassalle _{1,

2,

3} , Olivier J Manzoni _{1,

2,

3}

Affiliation

We investigated how metabotropic acetylcholine receptors control excitatory synaptic plasticity in the mouse nucleus accumbens core. Pharmacological and genetic approaches revealed that M1 mAChRs (muscarinic acetylcholine receptors) trigger multiple and interacting forms of synaptic plasticity. As previously described in the dorsal striatum, moderate pharmacological activation of M1 mAChR potentiated postsynaptic NMDARs. The M1-potentiation of NMDAR masked a previously unknown coincident TRPV1-mediated long-term depression (LTD). In addition, strong pharmacological activation of M1 mAChR induced canonical retrograde LTD, mediated by presynaptic CB1R. In the fmr1-/y mouse model of Fragile X, we found that CB1R but not TRPV1 M1-LTD was impaired. Finally, pharmacological blockade of the degradation of anandamide and 2-arachidonylglycerol, the two principal endocannabinoids restored fmr1-/y LTD to wild-type levels. These findings shed new light on the complex influence of acetylcholine on excitatory synapses in the nucleus accumbens core and identify new substrates of the synaptic deficits of Fragile X.

中文翻译：

毒蕈碱M1受体调节野生型和易碎X小鼠伏隔核突触可塑性。

我们调查了代谢型乙酰胆碱受体如何控制小鼠伏伏核的兴奋性突触可塑性。药理和遗传学方法表明，M1 mAChRs（毒蕈碱型乙酰胆碱受体）触发多种形式的相互作用的突触可塑性。如先前在背侧纹状体中所述，M1 mAChR增强的突触后NMDAR的中度药理活化。NMDAR的M1增强作用掩盖了以前未知的TRPV1介导的长期抑郁症（LTD）。此外，由突触前CB1R介导的M1 mAChR诱导的典型逆行LTD的强烈药理活化。在脆弱X的fmr1- / y小鼠模型中，我们发现CB1R受损，而TRPV1 M1-LTD没有受损。最终，药理学上阻断了花生四烯酸和2-花生四烯酸甘油的降解，这两个主要的内源性大麻素将fmr1- / y LTD恢复为野生型水平。这些发现为乙酰胆碱对伏伏核核心兴奋性突触的复杂影响提供了新的启示，并确定了脆性X突触缺陷的新底物。

更新日期：2018-02-28

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