M1 muscarinic acetylcholine receptor-mediated inhibition of GABA release from striatal medium spiny neurons onto cholinergic interneurons
M1 muscarinic acetylcholine receptor-mediated inhibition of GABA release from striatal medium spiny neurons onto cholinergic interneurons
复制标题
M1 毒蕈碱乙酰胆碱受体介导的 GABA 从纹状体中棘神经元释放到胆碱能中间神经元的抑制
DOI：
10.1111/ejn.15074
复制
发表时间：
2021
影响因子：
3.4
通讯作者：
Suzuki E & Momiyama T
中科院分区：
文献类型：
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作者：
Tamai Ryuichi;Igarashi Tasuku;Suzuki E & Momiyama T
乙酰胆碱（ACh）调节中枢神经系统中神经递质的释放。虽然GABA能传递到纹状体胆碱能中间神经元（ChIN）是由多巴胺受体调节，胆碱能调节相同的突触仍然是未知的。本研究采用光遗传学和全细胞膜片钳技术在幼年和青年小鼠脑片上研究了ACh在纹状体中型棘神经元（MSNs）向ChIN的GABA能传递中的调节作用。GABA A受体介导的抑制性突触后电流（IPSC）由局灶性电刺激或蓝光刺激诱发。在两个年龄组中，卡巴胆碱（一种毒蕈碱ACh受体激动剂）的浴用以浓度依赖性方式抑制IPSC的振幅。胆碱酯酶抑制剂毒扁豆碱也抑制IPSC的振幅。在存在膜渗透性M1毒蕈碱受体拮抗剂哌仑西平的情况下，卡巴胆碱诱导的IPSC抑制被拮抗，而M2毒蕈碱受体拮抗剂、M4受体拮抗剂或膜渗透性M1受体拮抗剂不能拮抗卡巴胆碱诱导的IPSC抑制。通过大麻素受体1的逆行大麻素级联反应不参与卡巴胆碱诱导的抑制。此外，卡巴胆碱并没有影响的内向电流的幅度所引起的烟雾应用GABA，而IPSCs的变异系数显着增加卡巴胆碱。这些结果表明，位于GABA能终末（包括MSNs细胞内细胞器）的突触前M1毒蕈碱受体的激活抑制了GABA释放到ChIN上。
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. GABAAreceptor‐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.