Distinct endocannabinoid control of GABA release at perisomatic and dendritic synapses in the hippocampus.
Distinct endocannabinoid control of GABA release at perisomatic and dendritic synapses in the hippocampus.
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DOI：
10.1523/jneurosci.6238-09.2010
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发表时间：
2010-06-09
期刊：
影响因子：
--
通讯作者：
Soltesz I
中科院分区：
文献类型：
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作者：
Lee SH;Földy C;Soltesz I
内源性大麻素介导的逆行突触信号是锥体细胞周围区突触释放GABA的关键调节剂，锥体细胞由共同表达大麻素1型受体（CB1R）和胆囊收缩素（CCK）的篮状细胞形成。然而，CB1R和CCK阳性GABA能末端也存在于锥体细胞树突上，但内源性大麻素控制树突中GABA释放的原理尚不清楚。我们对CCK阳性的体周细胞（篮状细胞）或树突突起细胞（Schaffer-collateral associated cells）中间神经元和突触后CA1锥体细胞进行配对记录，以确定gaba能突触沿躯体-树突轴的内源性大麻素信号传导特性。虽然目前已知的内源性大麻素合成分子机制的几个关键要素被认为主要定位于树突，但我们的研究结果显示，去极化诱导的抑制抑制（DSI），内源性大麻素介导的GABA释放的强直性抑制，以及代谢性谷氨酸受体激活诱导的CB1R介导的GABA释放的抑制在树突突触的效果都明显低于周围突触。此外，低浓度的外源性CB1受体激动剂对树突GABA释放的抑制程度低于细胞周围突触，这表明突触前差异是内源性大麻素对树突GABA释放的差异控制的部分原因。综上所述，这些数据证明了海马内源性大麻素信号对GABA释放的一种新的区域特异性调节。
Endocannabinoid mediated retrograde synaptic signaling is a key regulator of GABA release at synapses formed on the perisomatic region of pyramidal cells by basket cells that co-express the cannabinoid type 1 receptor (CB1R) and cholecystokinin (CCK). However, CB1R and CCK positive GABAergic terminals are present on pyramidal cell dendrites as well, but the principles of endocannabinoid control of GABA release in dendrites are not understood. We performed paired recordings from CCK positive perisomatically (basket cells) or dendritically projecting (Schaffer-collateral associated cells) interneurons and postsynaptic CA1 pyramidal cells to determine the properties of endocannabinoid signaling at GABAergic synapses along the somato-dendritic axis. Although several key elements of the currently known molecular machinery for endocannabinoid synthesis are thought be primarily localized in dendrites, our results revealed that the depolarization-induced suppression of inhibition (DSI), the endocannabinoid-mediated tonic inhibition of GABA release, and the metabotropic glutamate receptor activation induced, CB1R mediated depression of GABA release were all significantly less effective at dendritic compared to perisomatic synapses. In addition, low concentration of exogenous CB1 receptor agonist inhibited GABA release to a lesser extent at dendritic compared to perisomatic synapses, indicating that presynaptic differences are partly responsible for the differential control of GABA release by endocannabinoids in dendrites. Taken together, these data demonstrate a novel domain-specific regulation of GABA release by endocannabinoid signaling in the hippocampus.