The role of GABAergic signalling in neurodevelopmental disorders

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...

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Bibliographic Details
Published in:Nature reviews. Neuroscience 2021-05, Vol.22 (5), p.290-307
Main Authors: Tang, Xin, Jaenisch, Rudolf, Sur, Mriganka
Format: Article
Language:English
Subjects:
631/378/1689/2608
631/378/87
Animal Genetics and Genomics
Behavioral Sciences
Biological Techniques
Biomedical and Life Sciences
Biomedicine
Causes of
Cellular signal transduction
Child development deviations
Development and progression
Developmental disabilities
Etiology
GABA
GABAergic Neurons
gamma-Aminobutyric Acid
Genetic aspects
Health aspects
Humans
Nerve Net - physiopathology
Nervous system diseases
Neural circuitry
Neural networks
Neurobiology
Neurodevelopmental disorders
Neurodevelopmental Disorders - physiopathology
Neurodevelopmental Disorders - therapy
Neuroplasticity
Neurosciences
Precision Medicine
Review Article
Signal Transduction
Synapses
Synaptogenesis
γ-Aminobutyric acid
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Summary: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. Dysfunctional GABAergic signalling is common to various neurodevelopmental disorders (NDDs). Tang, Jaenisch and Sur give an overview of the contribution of GABA signalling dysfunction to NDD aetiology and examine how mechanistic insights into such disruption can be used to advance treatments for NDDs.
ISSN:1471-003X
1471-0048
1469-3178
DOI:10.1038/s41583-021-00443-x