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受体和细胞水平上抑制性信号的调节;我们对γ-氨基丁酸能神经传递及其在癫痫中被破坏机制的理解进展。

Regulation of Inhibitory Signaling at the Receptor and Cellular Level; Advances in Our Understanding of GABAergic Neurotransmission and the Mechanisms by Which It Is Disrupted in Epilepsy.

作者信息

Tipton Allison E, Russek Shelley J

机构信息

Graduate Program for Neuroscience, Boston University, Boston, MA, United States.

Biomolecular Pharmacology Program, Boston University School of Medicine, Boston, MA, United States.

出版信息

Front Synaptic Neurosci. 2022 Jun 15;14:914374. doi: 10.3389/fnsyn.2022.914374. eCollection 2022.

Abstract

Inhibitory signaling in the brain organizes the neural circuits that orchestrate how living creatures interact with the world around them and how they build representations of objects and ideas. Without tight control at multiple points of cellular engagement, the brain's inhibitory systems would run down and the ability to extract meaningful information from excitatory events would be lost leaving behind a system vulnerable to seizures and to cognitive decline. In this review, we will cover many of the salient features that have emerged regarding the dynamic regulation of inhibitory signaling seen through the lens of cell biology with an emphasis on the major building blocks, the ligand-gated ion channel receptors that are the first transduction point when the neurotransmitter GABA is released into the synapse. Epilepsy association will be used to indicate importance of key proteins and their pathways to brain function and to introduce novel areas for therapeutic intervention.

摘要

大脑中的抑制性信号传导构建了神经回路,这些回路协调着生物与周围世界的互动方式,以及它们如何构建物体和概念的表征。如果在细胞参与的多个环节没有严格控制,大脑的抑制系统就会衰退,从兴奋性事件中提取有意义信息的能力就会丧失,从而使系统容易出现癫痫发作和认知衰退。在这篇综述中,我们将探讨从细胞生物学角度观察到的抑制性信号动态调节所呈现的许多显著特征,重点关注主要组成部分,即配体门控离子通道受体,当神经递质γ-氨基丁酸(GABA)释放到突触中时,它是第一个转导点。癫痫关联将用于表明关键蛋白质及其通路对脑功能的重要性,并引入治疗干预的新领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad7/9302637/43eafc4b5dc4/fnsyn-14-914374-g001.jpg

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