Review article
The postnatal GABA shift: A developmental perspective

https://doi.org/10.1016/j.neubiorev.2021.01.024Get rights and content
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Highlights

  • The postnatal GABA shift is the last in a sequence of developmental GABA shifts.

  • The molecular mechanism for triggering the postnatal GABA shift remains unresolved.

  • Sensory input may be crucial in determining timing of the postnatal GABA shift.

  • The impact of GABA signaling is controlled by network activity and connectivity.

Abstract

GABA is the major inhibitory neurotransmitter that counterbalances excitation in the mature brain. The inhibitory action of GABA relies on the inflow of chloride ions (Cl), which hyperpolarizes the neuron. In early development, GABA signaling induces outward Cl currents and is depolarizing. The postnatal shift from depolarizing to hyperpolarizing GABA is a pivotal event in brain development and its timing affects brain function throughout life. Altered timing of the postnatal GABA shift is associated with several neurodevelopmental disorders. Here, we argue that the postnatal shift from depolarizing to hyperpolarizing GABA represents the final shift in a sequence of GABA shifts, regulating proliferation, migration, differentiation, and finally plasticity of developing neurons. Each developmental GABA shift ensures that the instructive role of GABA matches the circumstances of the developing network.

Sensory input may be a crucial factor in determining proper timing of the postnatal GABA shift. A developmental perspective is necessary to interpret the full consequences of a mismatch between connectivity, activity and GABA signaling during brain development.

Keywords

GABA
GABA polarity
Chloride
Chloride cotransporters
KCC2
NKCC1
Molecular mechanisms
Circuit formation
Brain development
Autism
Neurodevelopmental disorders

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