Welle Theresa M, Smith Katharine R
Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045, USA.
Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045, USA.
Curr Opin Neurobiol. 2025 Feb;90:102952. doi: 10.1016/j.conb.2024.102952. Epub 2024 Dec 25.
GABAergic synaptic inhibition controls circuit function by regulating neuronal plasticity, excitability, and firing. To achieve these goals, inhibitory synapses themselves undergo several forms of plasticity via diverse mechanisms, strengthening and weakening phasic inhibition in response to numerous activity-induced stimuli. These mechanisms include changing the number and arrangement of functional GABARs within the inhibitory postsynaptic domain (iPSD), which can profoundly regulate inhibitory synapse strength. Here, we explore recent advances in our molecular understanding of inhibitory postsynaptic plasticity, with a focus on modulation of the trafficking, protein-protein interactions, nanoscale-organization, and posttranscriptional regulation of GABARs and iPSD proteins. What has emerged is a complex mechanistic picture of how synaptic inhibition is controlled, with critical ramifications for cognition under typical and pathogenic conditions.
γ-氨基丁酸能（GABAergic）突触抑制通过调节神经元可塑性、兴奋性和放电来控制神经回路功能。为实现这些目标，抑制性突触自身通过多种机制经历几种形式的可塑性变化，以响应众多由活动诱导的刺激，增强和减弱相位性抑制。这些机制包括改变抑制性突触后结构域（iPSD）内功能性γ-氨基丁酸受体（GABARs）的数量和排列，这可深刻调节抑制性突触强度。在此，我们探讨了在分子层面上对抑制性突触后可塑性理解的最新进展，重点关注GABARs和iPSD蛋白的转运、蛋白质-蛋白质相互作用、纳米级组织以及转录后调控的调节。由此浮现出的是一幅关于突触抑制如何被控制的复杂机制图景，这对典型和致病条件下的认知具有关键影响。
