Perturbation of developmental Cl^-homeodynamics may underlie fetal and neonatal brain disorders

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The most major inhibitory neurotransmitter, GABA, induces synaptic inhibition in the adult brain. In immature neurons, however,[ Cl^-]_i is high due to balance of Cl^-transporters, promoting depolarizing GABA action by efflux of Cl^-along with its electrical gradient. Thus GABA evokes excitation and/or non-synaptic tonic depolarization in immature brain. Such multimodal GABA actions during development are necessary for neurogenesis, differentiation, migration, and synaptogenesis. Therfore, perturbation of the developmental Cl^-homeodynamics may underlie fetal and neonatal brain disorders. By using various pathological model mice, we have studied how Cl^-homeodynamics work in pathogenesis of fetal and neonatal disorders of cortical development.