The postnatal GABA shift: A developmental perspective

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.

Automated summary

The transition from depolarizing to hyperpolarizing GABA signaling during postnatal development is crucial for brain function and associated with neurodevelopmental disorders. Each developmental shift in GABA function regulates different aspects of neuron development, ensuring alignment with the developing network environment. Proper timing of the postnatal GABA shift may be influenced by sensory input and a developmental perspective is needed to understand the consequences of mismatches in connectivity, activity, and GABA signaling during brain development.