Distinct 5-HT receptor subtypes regulate claustrum excitability by serotonin and the psychedelic, DOI

IF 6.7 2区医学 Q1 NEUROSCIENCES

Progress in Neurobiology Pub Date : 2024-09-01 DOI:10.1016/j.pneurobio.2024.102660

Tanner L. Anderson , Jack V. Keady , Judy Songrady , Navid S. Tavakoli , Artin Asadipooya , Ryson E. Neeley , Jill R. Turner , Pavel I. Ortinski

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引用次数: 0

Abstract

Recent evidence indicates that neuronal activity within the claustrum (CLA) may be central to cellular and behavioral responses to psychedelic hallucinogens. The CLA prominently innervates many cortical targets and displays exceptionally high levels of serotonin (5-HT) binding. However, the influence of serotonin receptors, prime targets of psychedelic drug action, on CLA activity remains unexplored. We characterize the CLA expression of all known 5-HT subtypes and contrast the effects of 5-HT and the psychedelic hallucinogen, 2,5-dimethoxy-4-iodoamphetamine (DOI), on excitability of cortical-projecting CLA neurons. We find that the CLA is particularly enriched with 5-HT2C receptors, expressed predominantly on glutamatergic neurons. Electrophysiological recordings from CLA neurons that project to the anterior cingulate cortex (ACC) indicate that application of 5-HT inhibits glutamate receptor-mediated excitatory postsynaptic currents (EPSCs). In contrast, application of DOI stimulates EPSCs. We find that the opposite effects of 5-HT and DOI on synaptic signaling can both be reversed by inhibition of the 5-HT2C, but not 5-HT2A, receptors. We identify specific 5-HT receptor subtypes as serotonergic regulators of the CLA excitability and argue against the canonical role of 5-HT2A in glutamatergic synapse response to psychedelics within the CLA-ACC circuit.

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不同的 5-HT 受体亚型受血清素和迷幻药的影响而调节视网膜的兴奋性，DOI.

最近的证据表明，鼓室（CLA）内的神经元活动可能是细胞和行为对迷幻致幻剂反应的核心。CLA主要支配大脑皮层的许多目标，并显示出极高水平的血清素（5-HT）结合。然而，5-羟色胺受体（迷幻药的主要作用靶点）对CLA活性的影响仍有待探索。我们描述了所有已知 5-HT 亚型的 CLA 表达，并对比了 5-HT 和迷幻致幻剂 2,5-二甲氧基-4-碘苯丙胺（DOI）对皮质投射 CLA 神经元兴奋性的影响。我们发现，CLA 特别富含 5-HT2C 受体，主要表达在谷氨酸能神经元上。对投射到前扣带回皮层（ACC）的CLA神经元进行的电生理记录表明，施加5-HT会抑制谷氨酸受体介导的兴奋性突触后电流（EPSC）。相反，应用 DOI 则会刺激 EPSC。我们发现，5-HT 和 DOI 对突触信号转导的相反作用都可以通过抑制 5-HT2C 而非 5-HT2A 受体来逆转。我们确定了特定的 5-HT 受体亚型是 CLA 兴奋性的血清素能调节器，并反驳了 5-HT2A 在 CLA-ACC 回路中谷氨酸能突触对迷幻药反应的典型作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Progress in Neurobiology 医学-神经科学

CiteScore

12.80

自引率

1.50%

发文量

107

审稿时长

33 days

期刊介绍： Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.