Localization and developmental expression patterns of the neuronal K-Cl cotransporter (KCC2) in the rat retina

The processing of signals by integrative neurons in the retina and CNS reli es strongly on inhibitory synaptic inputs, principally from GABAergic and g lycinergic neurons that serve primarily to hyperpolarize postsynaptic neuro ns. Recent evidence indicates that the neuron-specific K-Cl cotransporter 2 (KCC2) is the major chloride extrusion system permitting hyperpolarizing i nhibitory responses. It has been hypothesized that depolarizing GABA respon ses observed in immature neurons are converted to hyperpolarizing responses in large part by the expression of KCC2 during the second week of postnata l development. The cell-specific localization and developmental expression of KCC2 protein have been examined in relatively few neural tissues and hav e never been studied in retina, of which much is known physiologically and morphologically about inhibitory synaptic circuits. We examined the localiz ation of KCC2 in adult rat retina with immunohistochemical techniques and d etermined the time course of its postnatal expression. KCC2 expression was localized in horizontal cells, bipolar cells, amacrine cells, and, most lik ely, ganglion cells, all of which are known to express GABA receptor subtyp es. Developmentally, KCC2 expression in the retina increased gradually from postnatal day 1 (P1) until P14 in the inner retina, whereas expression was delayed in the outer plexiform layer until P7 but reached its adult level by P14. These data support the hypothesis that the function of KCC2 is inti mately involved in GABAergic synaptic processing. Furthermore, the delayed temporal expression of KCC2 in the outer plexiform layer indicates that GAB Aergic function may be differentially regulated in retina during postnatal development and that GABA may produce depolarizing responses in the outer p lexiform layer at times when it generates hyperpolarizing responses in the inner plexiform layer.