Heterogeneous Expression of the Potassium-Chloride Cotransporter KCC₂ in Gonadotropin-Releasing Hormone Neurons of the Adult Mouse

Abstract

In mature central neurons, chloride extrusion mediated by the K-Cl cotransporter KCC₂ appears to be largely responsible for the Cl− driving force that allows γ-aminobutyric acidA (GABAA) receptor activation to trigger a hyperpolarization. In its absence, GABA’s effect is typically depolarizing and often excitatory. We examined the colocalization of KCC₂ and GnRH in adult male and female mice using a combined in situ hybridization-immunofluorescence procedure. We found that KCC₂ was localized to approximately 34% of GnRH neurons. This proportion was similar in females and males. However, females exhibited a marked rostrocaudal gradient of colocalization that was not seen in males. By contrast, KCC₂ was localized to nearly all vasopressin neurons of the supraoptic nucleus. These results indicate that a substantial fraction of GnRH neurons may be depolarized and excited by GABAA receptor activation throughout life, supporting the existence of functionally heterogeneous subpopulations.