Role of KCC2 in Neuronal Plasticity

GABA is the principal inhibitory neurotransmitter in the adult brain. However, at early developmental stages, through the second postnatal week in rodent, GABA acting via chloride-permeable GABAAR channels exerts paradoxical depolarizing and excitatory action on the immature neurons. The depolarizing action of GABA is due to the elevated intracellular chloride concentration in the immature neurons which in turn is due to the prolonged postnatal development of the chloride homeostasis system, most notably the potassium-chloride co-transporter KCC2. The main finding of the present work is that in addition to its usual role, the potassium chloride co-transporter KCC2 exerts an active role in formation of the neuronal network. The second major conclusion is that the overexpression of KCC2 in cultured hippocampal neurons has neuroprotective effect. These results allow reconsidering the importance of numerous previous findings that definitely will help in understanding of the organization of developing brain.