Chloride homeodynamics underlying modal shifts in cellular and network oscillations.

Abstract:

:γ-Aminobutyric acid (GABA) generally induces hyperpolarization and inhibition in the adult brain, but causes depolarization (and can be excitatory) in the immature brain. Depolarizing GABA actions are necessary for neurogenesis, differentiation, migration, and synaptogenesis. Additionally, the conversion of GABA responses from inhibition to excitation can be induced in adults by pathological conditions. Because GABAA receptors are Cl- channels, alternating GABA actions between hyperpolarization (Cl- influx) and depolarization (Cl- efflux) are induced by changes in the Cl- gradient, which is regulated by C- transporters. Thus, the dynamics of neural functions are modulated by active Cl- homeostasis (Cl- homeodynamics), alternating inhibition and excitation, and could underlie the modal shifts in cellular and network oscillations. Such a modal shift in GABA actions is required for normal development. Thus disturbances in this developmental GABA modal shift and/or the induction of excitatory GABA action in adult could underlie the pathogenesis of diverse neurological diseases (so-called network diseases).

journal_name

Neurosci Res

journal_title

Neuroscience research

authors

Fukuda A

doi

10.1016/j.neures.2020.02.010

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

14-23

eissn

0168-0102

issn

1872-8111

pii

S0168-0102(19)30717-5

journal_volume

156

pub_type

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