Acetylcholine (ACh) modulates neurotransmitter release in the central nervous system. Although GABAergic transmission onto the striatal cholinergic interneurons (ChIN) is modulated by dopamine receptors, cholinergic modulation of the same synapse is still unknown. In the present study, modulatory roles of ACh in the GABAergic transmission from striatal medium spiny neurons (MSNs) onto ChIN were investigated using optogenetics and whole‐cell patch‐clamp technique in juvenile and young‐adult mice brain slices. GABA_A receptor‐mediated inhibitory postsynaptic currents (IPSCs) were evoked by focal electrical‐ or blue‐light stimulation. Bath application of carbachol, a muscarinic ACh receptor agonist, suppressed the amplitude of IPSCs in a concentration‐dependent manner in both age groups. A choline esterase inhibitor, physostigmine, also suppressed the amplitude of IPSCs. In the presence of a membrane permeable M1 muscarine receptor antagonist, pirenzepine, carbachol‐induced suppression of IPSCs was antagonized, whereas a M2 muscarine receptor antagonist, a M4 receptor antagonist, or a membrane impermeable M1 receptor antagonist did not antagonize carbachol‐induced suppression of IPSCs. Retrograde cannabinoid cascade via cannabinoid receptor 1 was not involved in carbachol‐induced inhibition. Furthermore, carbachol did not affect amplitude of inward currents induced by puff application of GABA, whereas coefficient of variation of IPSCs was significantly increased by carbachol. These results suggest that activation of presynaptic M1 muscarine receptors located on the GABAergic terminals including intracellular organelle of MSNs inhibits GABA release onto ChIN.

中文翻译：

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M1毒蕈碱乙酰胆碱受体介导的抑制纹状体中棘神经元释放GABA到胆碱能中间神经元

乙酰胆碱（ACh）调节中枢神经系统中神经递质的释放。尽管GABA能传递到纹状体胆碱能神经元（ChIN）上是由多巴胺受体调节的，但同一突触的胆碱能调节仍是未知的。在本研究中，使用光遗传学和全细胞膜片钳技术研究了ACh在从纹状体中棘神经元（MSNs）传递到ChIN的GABA能传递中的调节作用。GABA _A局部电刺激或蓝光刺激诱发了受体介导的突触后抑制电流（IPSC）。在两个年龄组中，对毒蕈碱型ACh受体激动剂卡巴胆碱的沐浴应用均以浓度依赖的方式抑制了IPSC的振幅。胆碱酯酶抑制剂毒扁豆碱也可以抑制IPSC的振幅。在存在膜渗透性M1毒蕈碱受体拮抗剂，哌仑西平时，拮抗了卡巴胆碱对IPSCs的抑制作用，而M2毒蕈碱受体拮抗剂，M4受体拮抗剂或膜不渗透性M1受体拮抗剂却没有拮抗卡巴胆碱对IPSCs的抑制作用。 IPSC。通过大麻素受体1逆行的大麻素级联反应与卡巴胆碱诱导的抑制作用无关。此外，卡巴胆碱不影响通过抽吸GABA诱导的内向电流幅度，而卡巴胆碱显着增加了IPSCs的变异系数。这些结果表明，位于MSAs胞内细胞器等GABA能端上的突触前M1毒蕈碱受体的激活抑制了GABA释放到ChIN上。