Document Type

Article

Publication Date

6-26-2019

Publication Title

Frontiers in Molecular Neuroscience

Volume

12

Issue

154

First page number:

1

Last page number:

9

Abstract

The diversity of inhibitory interneurons allows for the coordination and modulation of excitatory principal cell firing. Interneurons that release GABA (γ-aminobutyric acid) onto the soma and axon exert powerful control by virtue of proximity to the site of action potential generation at the axon initial segment (AIS). Here, we review and examine the cellular and molecular regulation of soma and axon targeting GABAergic synapses in the cortex and hippocampus. We also describe their role in controlling network activity in normal and pathological states. Recent studies have demonstrated a specific role for postsynaptic dystroglycan in the formation and maintenance of cholecystokinin positive basket cell terminals contacting the soma, and postsynaptic collybistin in parvalbumin positive chandelier cell contacts onto the AIS. Unique presynaptic molecular contributors, LGI2 and FGF13, expressed in parvalbumin positive basket cells and chandelier cells, respectively, have also recently been identified. Mutations in the genes encoding proteins critical for somatic and AIS inhibitory synapses have been associated with human disorders of the nervous system. Dystroglycan dysfunction in some congenital muscular dystrophies is associated with developmental brain malformations, intellectual disability, and rare epilepsy. Collybistin dysfunction has been linked to hyperekplexia, epilepsy, intellectual disability, and developmental disorders. Both LGI2 and FGF13 mutations are implicated in syndromes with epilepsy as a component. Advancing our understanding of the powerful roles of somatic and axonic GABAergic contacts in controlling activity patterns in the cortex and hippocampus will provide insight into the pathogenesis of epilepsy and other nervous system disorders.

Keywords

GABAergic synapse development; Epilepsies and epileptic syndromes; Cholecystokinin; Parvalbumin; Interneuron; GABAA receptor subunits; Somatic inhibitory synapse; Axon initial segment inhibitory synapse

Disciplines

Molecular and Cellular Neuroscience

File Format

pdf

File Size

1459 KB

Language

English

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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