Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Boston Children's Hospital, Boston, MA, USA.
Nat Rev Neurosci. 2021 May;22(5):290-307. doi: 10.1038/s41583-021-00443-x. Epub 2021 Mar 26.
GABAergic inhibition shapes the connectivity, activity and plasticity of the brain. A series of exciting new discoveries provides compelling evidence that disruptions in a number of key facets of GABAergic inhibition have critical roles in the aetiology of neurodevelopmental disorders (NDDs). These facets include the generation, migration and survival of GABAergic neurons, the formation of GABAergic synapses and circuit connectivity, and the dynamic regulation of the efficacy of GABAergic signalling through neuronal chloride transporters. In this Review, we discuss recent work that elucidates the functions and dysfunctions of GABAergic signalling in health and disease, that uncovers the contribution of GABAergic neural circuit dysfunction to NDD aetiology and that leverages such mechanistic insights to advance precision medicine for the treatment of NDDs.
GABA 能抑制塑造了大脑的连接、活动和可塑性。一系列令人兴奋的新发现提供了令人信服的证据，表明 GABA 能抑制的许多关键方面的中断在神经发育障碍 (NDD) 的发病机制中起着关键作用。这些方面包括 GABA 能神经元的产生、迁移和存活、GABA 能突触和回路连接的形成，以及通过神经元氯离子转运体对 GABA 能信号传递效率的动态调节。在这篇综述中，我们讨论了最近阐明 GABA 能信号在健康和疾病中的功能和失调、揭示 GABA 能神经回路功能障碍对 NDD 发病机制的贡献，并利用这些机制见解推进治疗 NDD 的精准医学的工作。
