5-HT1A Receptor-Mediated Autoinhibition and the Control of Serotonergic Cell Firing.
5-HT1A Receptor-Mediated Autoinhibition and the Control of Serotonergic Cell Firing.
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DOI：
10.1021/acschemneuro.5b00034
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发表时间：
2015-07-15
影响因子：
5
通讯作者：
McGregor KM
中科院分区：
文献类型：
--
作者：
Andrade R;Huereca D;Lyons JG;Andrade EM;McGregor KM
多巴胺能突触传递在情绪控制以及焦虑和抑郁的药物治疗中起着重要作用的观点是现代生物精神病学的基石之一。因此，有强烈的兴趣，了解机制控制的活性，合成的阿托宁（阿托宁能）神经元。这项工作中出现的最古老和最持久的想法之一是，多巴胺能神经元能够自主调节自己的基础放电率。5-羟色胺能神经元在其表面上表达5-HT 1A受体（自身受体），当其被激活时，诱导钾通道的开放，钾通道过度兴奋，从而抑制细胞放电。多巴胺能神经核内5-羟色胺的活性依赖性释放被认为激活这些自身受体，从而完成自身抑制反馈回路。这一概念最初于20世纪70年代提出，已被证明是非常富有成效的，并指导了广泛的临床和临床前工作的解释。然而，值得注意的是，寻求直接证明这一现象的电生理学研究，特别是在体外脑切片中，产生了混合的结果。在这里，我们批判性地回顾这项工作，重点是电生理研究，直接评估神经元的活动。我们还强调了最近的工作表明，5-HT 1A受体介导的自抑制可能发挥其他作用，除了作为一个反馈调节器的起搏器样放电率的神经元的放电控制。
The idea that serotonergic synaptic transmission plays an essential role in the control of mood and the pharmacotherapy of anxiety and depression is one of the cornerstones of modern biological psychiatry. As a result, there is intense interest in understanding the mechanisms controlling the activity of serotonin-synthesizing (serotonergic) neurons. One of the oldest and most durable ideas emerging from this work is that serotonergic neurons are capable of autonomously regulating their own basal firing rate. Serotonergic neurons express on their surface 5-HT1A receptors (autoreceptors) that, when activated, induce the opening of potassium channels that hyperpolarize and thereby inhibit cell firing. Activity-dependent release of serotonin within serotonergic nuclei is thought to activate these autoreceptors, thus completing an autoinhibitory feedback loop. This concept, which was originally proposed in the 1970s, has proven to be enormously fruitful and has guided the interpretation of a broad range of clinical and preclinical work. Yet, remarkably, electrophysiological studies seeking to directly demonstrate this phenomenon, especially in in vitro brain slices, have produced mixed results. Here, we critically review this work with a focus on electrophysiological studies, which directly assess neuronal activity. We also highlight recent work suggesting that 5-HT1A receptor-mediated autoinhibition may play other roles in the control of firing besides acting as a feedback regulator for the pacemaker-like firing rate of serotonergic neurons.