Brief trains of action potentials enhance pyramidal neuron excitability via endocannabinoid-mediated suppression of inhibition
Brief trains of action potentials enhance pyramidal neuron excitability via endocannabinoid-mediated suppression of inhibition
复制标题
DOI：
10.1152/jn.00351.2004
复制
发表时间：
2004-10-01
影响因子：
2.5
通讯作者：
Levine, ES
中科院分区：
文献类型：
--
作者：
Fortin, DA;Trettel, J;Levine, ES
去极化诱导的抑制抑制（DSI）是GABA能突触上的一种逆行信号传导形式，由突触后神经元释放的内源性大麻素的钙离子和去极化依赖性引发。在新皮层中，锥体神经元（PN）似乎使用DSI作为一种机制，用于调节表达1型大麻素受体的GABA能输入亚群的体细胞抑制。虽然传入抑制的突触后控制可能会直接影响新皮层PNs的综合性能，很少有人知道的活动模式，引起内源性大麻素的释放和这种去抑制可能对PNs的兴奋性的影响。在这里，我们提供了第一个系统的调查动作电位（AP）诱导的DSI在新皮层。DSI的幅度和时间过程是直接相关的突触后AP的数量和频率与显着的抑制所引起的20 Hz的火车包含少至三个AP。这种AP诱导的DSI由内源性大麻素介导，因为它被大麻素受体拮抗剂AM251阻止并被内源性大麻素转运抑制剂AM404增强。我们还探讨了内源性大麻素介导的DSI对PN兴奋性的影响。我们发现，单一的AP串明显增加PN对兴奋性突触输入的反应性，并通过抑制GABA能抑制而促进AP放电。这种作用的时间过程抑制DSI表达，并被AM 251完全阻断。两者合计，我们的数据表明内源性大麻素在调节皮质PN输出的作用。
Depolarization-induced suppression of inhibition (DSI) is a form of retrograde signaling at GABAergic synapses that is initiated by the calcium- and depolarization-dependent release of endocannabinoids from postsynaptic neurons. In the neocortex, pyramidal neurons (PNs) appear to use DSI as a mechanism for regulating somatic inhibition from a subpopulation of GABAergic inputs that express the type 1 cannabinoid receptor. Although postsynaptic control of afferent inhibition may directly influence the integrative properties of neocortical PNs, little is known about the patterns of activity that evoke endocannabinoid release and the impact such disinhibition may have on the excitability of PNs. Here we provide the first systematic survey of action potential (AP)-induced DSI in the neocortex. The magnitude and time course of DSI was directly related to the number and frequency of postsynaptic APs with significant suppression induced by a 20-Hz train containing as few as three APs. This AP-induced DSI was mediated by endocannabinoids as it was prevented by the cannabinoid receptor antagonist AM251 and potentiated by the endocannabinoid transport inhibitor AM404. We also explored the effects of endocannabinoid-mediated DSI on PN excitability. We found that single AP trains markedly increased PN responsiveness to excitatory synaptic inputs and promoted AP discharge by suppressing GABAergic inhibition. The time course of this effect paralleled DSI expression and was completely blocked by AM251. Taken together, our data suggest a role for endocannabinoids in regulating the output of cortical PNs.