Differential development of cation-chloride cotransporters and Cl- homeostasis contributes to differential GABAergic...

A recent study suggested that gamma-aminobutyric acid (GABA) plays differential roles in activity-dependent plasticity between the visual cortex (VC) and the dorsal lateral geniculate nucleus (dLGN). In the present study, to investigate differential GABAergic functions in postnatal visual system development, the development of [Cl(-)](i), cation-Cl(-) cotransporter expression, and the [Ca(2+)](i) responses evoked by GABA were compared between VC and dLGN during the early stages of development. Using rat brain slices from postnatal days (P) 0-17, GABA-evoked [Ca(2+)](i) responses and resting [Cl(-)](i) were measured by means of optical imaging of Ca(2+) and Cl(-), respectively. Changes in the expression of cation-Cl(-) cotransporters (viz. the outwardly-directed K(+)-Cl(-) cotransporter, KCC2, and the inwardly-directed Na(+),K(+)-2Cl(-) cotransporter, NKCC1) were examined in VC and dLGN by in situ hybridization. At birth, the excitatory actions of GABA were powerful in VC, but missing in dLGN (as indicated by neuronal [Ca(2+)](i) transients), and the resting [Cl(-)](i) was significantly higher in VC than in dLGN. Signals for KCC2 mRNA expression were significantly higher in dLGN than in VC at P0. This suggests that extrusion of Cl(-) from neurons is stronger in dLGN than in VC at P0, so that a GABAergic excitatory effect was not observed in dLGN because of more negative equilibrium potential for Cl(-). The present study indicates clear differences in the molecular and physiological bases of Cl(-) homeostasis and GABA actions between the developing VC and dLGN. Such differential GABAergic actions may underlie the distinct mechanisms involved in VC and dLGN development within the visual system.