Environmental influences on cortical development and plasticity via Cl^-homeostasis modulation

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The aim of this study is to examine a validity of the hypothesis that a programmed Cl^- homeostasis of the developmental period renders GABA excitatory and promotes corticogenesis by cell migration, and that its change by environmental stimulation influence the neural circuit formation and plasticity. We established a method to distinguish between radially-migrating glutamate cells and tangentially-migrating GABA cells in living slices, by means of transfection of the HcRed gene into a GAD67-GFP knock-in mouse embryo brain in vivo. Taurine, abundantly contained in embryo brains, might act as autocrine endogenous agonist of GABA_A receptors for radial migration, and might also act as paracrine agonist for a signal to tangential migration. As for transfected ectopic KCC2, it was suggested that it did not function in vivo during radial migration. Therefore, we have designed the base sequence which was most suitable for shRNA which interfere a transcription process of a Cl^- transporter, a … More nd constructed an expression plasmid vector encoding it. Regarding the communication within the marginal zone containing the Cajal-Retzius cells which play an important role in radial migration, GABA and taurine worked as endogenous agonists of GABA_A and glycine receptors, respectively, that promoted a spread of excitation within the marginal zone. GABA_A and the glycine receptors, that were originally inhibitory, increased an excitability due to high [Cl^-]_i what was maintained by NKCC1. However, glutamate receptors which are originally excitatory did not participate. Considering maternal stress as environmental stimulation for embryos, we developed a mouse model of restriction stress to a mother, which were confined in a cylinder of 3cm diameter and 9cm in length for six hours/day from 8th to 17th gestational days. Both the body weight and the brain weight of embryos at day 18th were significantly decreased in comparison with control, indicating an influence to the embryonic brain development by maternal stress. Less