The postnatal GABA shift: A developmental perspective

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:124

Review

Peerboom, Carlijn¹  Wierenga, Corette J.¹ 

[1] Univ Utrecht, Fac Sci, Biol Dept, Cell Biol Neurobiol & Biophys, NL-3584 CH Utrecht, Netherlands

关键词: GABA;    GABA polarity;    Chloride;    Chloride cotransporters;    KCC2;    NKCC1;    Molecular mechanisms;    Circuit formation;    Brain development;    Autism;    Neurodevelopmental disorders;   

DOI  :  10.1016/j.neubiorev.2021.01.024

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free