Asynchronous release of GABA via tonic cannabinoid receptor activation at identified interneuron synapses in rat CA1
Asynchronous release of GABA via tonic cannabinoid receptor activation at identified interneuron synapses in rat CA1
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DOI：
10.1111/j.1460-9568.2010.07165.x
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发表时间：
2010-04-01
影响因子：
3.4
通讯作者：
Todorova，M.
中科院分区：
文献类型：
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作者：
Ali，A. B.;Todorova，M.
局部回路中间神经元的影响被认为通过内源性大麻素1型（CB 1）受体在调节突触强度中起重要作用。 使用成对的全细胞记录，结合出生后第18-23天大鼠CA 1急性切片的双重免疫荧光和生物胞素标记，我们研究了利用CB 1受体的胆囊收缩素（CCK）阳性放射层局部回路中间神经元连接的特性。 研究了三种类型的突触连接，陷窝-分子-辐射穿通路径相关（LM-R PPA）到Shaffer侧支相关（SCA）中间神经元，SCA-SCA中间神经元和SCA-锥体细胞。 这三个突触在抑制的紧张性降低下有差异，该抑制被CB 1受体反向激动剂AM-251（10 μm）阻断，这增强了IPSP。 抑制的紧张性减少的强度与异步释放，这是明显的中间神经元之间的连接。AM-251增加了同步与异步释放的比率（同步性比率），而CB受体激动剂花生四烯酸（14 μm）降低了同步性比率。 快速和慢速钙螯合剂（BAPTA-AM和EGTA-AM）也增加了同步性比率，加速了抑制时间进程并降低了IPSP振幅。这些数据表明，CB 1受体之间的连接神经元突触起着重要的作用，在紧张性抑制抑制和管理的GABA的异步释放，调节抑制的时间窗口。钙螯合剂的作用表明，非同步释放是突触前钙瞬变和/或钙源与胞吐传感器之间距离较远的结果。这些特性的专门抑制神经元可能有重要的调制作用，在控制当地的电路中间神经元之间的尖峰时间。
The influence of local circuit interneurons is thought to play an important role in adjusting synaptic strength via endogenous cannabinoid type 1 (CB1) receptors. Using paired whole‐cell recordings, combined with double immunofluorescence and biocytin labelling in acute slices of rat CA1 at postnatal day 18–23, we investigated the properties of Cholecystokinin (CCK)‐positive stratum radiatum local circuit interneuron connections that utilised CB1 receptors. Three types of synaptic connections were studied, lacunosum‐moleculare‐radiatum perforant path‐associated (LM‐R PPA) to Shaffer collateral‐associated (SCA) interneurons, SCA–SCA interneurons and SCA–pyramidal cells. These three synapses were differentially under tonic reduction of inhibition that was blocked by the CB1 receptor inverse agonist AM‐251 (10 μm), which enhanced IPSPs. The strength of tonic reduction of inhibition was correlated with asynchronous release which was apparent at connections among interneurons. AM‐251 increased the ratio of synchronous to asynchronous release (synchronicity ratio), while the CB receptor agonist anandamide (14 μm) decreased the synchronicity ratio. Fast and slow calcium chelators (BAPTA‐AM and EGTA‐AM) also increased the synchronicity ratio, accelerated inhibitory time courses and reduced IPSP amplitudes. These data suggest that CB1 receptors at connections among interneuron synapses play a role in tonic suppression of inhibition and govern the asynchronous release of GABA, modulating the time windows of inhibition. Effects of calcium chelators suggest that asynchronous release is a result of a long‐lasting presynaptic calcium transients and/or a large distance between calcium source and sensor of exocytosis. These properties of specialised inhibitory neurons may have important modulatory roles in controlling spike timing among local circuit interneurons.