Reciprocal regulation of inhibitory synaptic transmission by nicotinic and muscarinic receptors in rat nucleus accumbens shell.
Reciprocal regulation of inhibitory synaptic transmission by nicotinic and muscarinic receptors in rat nucleus accumbens shell.
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大鼠伏隔核壳中烟碱和毒蕈碱受体对抑制性突触传递的相互调节。
DOI：
10.1113/jphysiol.2013.258558
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kobayashi M
中科院分区：
文献类型：
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作者：
Yamamoto K;Ebihara K;Koshikawa N;Kobayashi M
要点•虽然胆碱能中间神经元数量很少，但它们的轴突密集神经支配，并在伏隔核（NAc）中提供丰富的含乙酰胆碱末端。•虽然已报道通过烟碱和毒蕈碱受体对抑制性突触后电流（IPSC）产生胆碱能作用，但IPSC的胆碱能调节与NAc中的突触前细胞亚型之间的关系仍然难以捉摸。•这里我们表明，毒蕈碱受体激活抑制中型多棘神经元（MSN）→MSN 连接中的 IPSC，而烟碱受体激活则增强快速尖峰神经元→MSN 连接中的 IPSC。•IPSC 的这些相互调节机制有助于我们了解胆碱能过程在 NAc 的生理和病理生理功能中的作用。伏隔核 (NAc) 是主要神经元，其活动受到来自 MSN 和快速尖峰中间神经元 (FSN) 的 GABA 能输入的调节。胆碱能中间神经元在 MSN 活动的调节中发挥重要作用；然而，乙酰胆碱如何调节从 MSNs/FSNs 到 MSNs 的抑制性突触传递仍然未知。我们对大鼠 NAc 壳切片制剂中的 MSN 和 FSN 进行配对全细胞膜片钳记录，并检查了胆碱能对单一抑制性突触后电流 (uIPSC) 的影响。卡巴胆碱 (1 μm) 将 MSN→MSN 连接中的 uIPSC 振幅抑制了 58.3 ± 8.0%，伴随着配对脉冲比和故障率的增加，表明乙酰胆碱降低了 MSN 突触末端释放 GABA 的可能性。卡巴胆碱诱导的 uIPSC 抑制被 100 μm 马托品拮抗，并被毛果芸香碱 (1 μm) 和乙酰胆碱 (1 μm) 模拟，但不被尼古丁 (1 μm) 模拟。 AM251 的应用略微降低了卡巴胆碱诱导的 uIPSC 抑制（30.8 ± 8.9%），表明内源性大麻素信号传导参与了 uIPSC 的毒蕈碱抑制。相反，FSN→MSN 连接表明毛果芸香碱对 uIPSC 振幅影响不大，而尼古丁和乙酰胆碱均促进 uIPSC 振幅，且失败率和配对脉冲比降低，表明尼古丁诱导的 uIPSC 促进是由突触前机制介导的。微型 IPSC 记录支持这些突触前胆碱能机制的假设。这些结果表明毒蕈碱受体和烟碱受体在 GABA 释放中的不同作用，这取决于 NAc 壳中的突触前神经元亚型。
Key points•While cholinergic interneurones are few in number, their axons densely innervate and provide abundant acetylcholine‐containing terminals in the nucleus accumbens (NAc).•Although cholinergic effects on inhibitory postsynaptic currents (IPSCs) via nicotinic and muscarinic receptors have been reported, the relationship between cholinergic modulation of IPSCs and presynaptic cell subtypes in the NAc has remained elusive.•Here we show that muscarinic receptor activation suppresses IPSCs in medium spiny neurone (MSN)→MSN connections, whereas nicotinic receptor activation enhances IPSCs in fast‐spiking neurone→MSN connections.•These reciprocal regulatory mechanisms for IPSCs help us to understand the role of cholinergic processes in physiological and pathophysiological functions of the NAc.AbstractMedium spiny neurones (MSNs) in the nucleus accumbens (NAc) are the principal neurones whose activities are regulated by GABAergic inputs from MSNs and fast‐spiking interneurones (FSNs). Cholinergic interneurones play important roles in the regulation of activity in MSNs; however, how acetylcholine modulates inhibitory synaptic transmission from MSNs/FSNs to MSNs remains unknown. We performed paired whole‐cell patch‐clamp recordings from MSNs and FSNs in rat NAc shell slice preparations and examined cholinergic effects on unitary inhibitory postsynaptic currents (uIPSCs). Carbachol (1 μm) suppressed uIPSC amplitude by 58.3 ± 8.0% in MSN→MSN connections, accompanied by increases in paired‐pulse ratio and failure rate, suggesting that acetylcholine reduces the probability of GABA release from the synaptic terminals of MSNs. Carbachol‐induced uIPSC suppression was antagonised by 100 μmatropine, and was mimicked by pilocarpine (1 μm) and acetylcholine (1 μm) but not nicotine (1 μm). Application of AM251 slightly reduced carbachol‐induced uIPSC suppression (30.8 ± 8.9%), suggesting an involvement of endocannabinoid signalling in muscarinic suppression of uIPSCs. In contrast, FSN→MSN connections showed that pilocarpine had little effect on the uIPSC amplitude, whereas both nicotine and acetylcholine facilitated uIPSC amplitude, with decreases in failure rate and paired‐pulse ratio, suggesting that nicotine‐induced uIPSC facilitation is mediated by presynaptic mechanisms. Miniature IPSC recordings support these hypotheses of presynaptic cholinergic mechanisms. These results suggest a differential role for muscarinic and nicotinic receptors in GABA release, which depends on presynaptic neuronal subtypes in the NAc shell.