The role of excitatory action of GABA in the estrous cycle of mouse

促性腺激素释放激素（GnRH）神经元形成了生殖中枢调控的最终共同途径。在此之前，我们报道了成人大脑中主要的抑制性神经递质GABA在成人GnRH神经元中发挥兴奋作用。为了研究GABA在体内GnRH神经元中兴奋作用的功能作用，我们使用四环素控制的基因表达系统，以可逆的方式产生了KCC2条件过表达或NKCC1基因敲除的转基因小鼠，这些小鼠在GnRH神经元中受到限制。在GnRH神经元中表达KCC2的雌性小鼠未妊娠，且出现异常的发情周期，卵巢异常，有许多小卵泡。这些结果表明，GABA对GnRH神经元的兴奋作用在雌性生殖中具有重要作用。

Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for the central regulation of reproduction. Previously, we reported that GABA, the main inhibitory neurotransmitter in the adult brain, exerts an excitatory action in adult GnRH neurons. To examine the functional role of the excitatory action of GABA in GnRH neurons in vivo, we generated transgenic mice with conditional overexpression of KCC2 or knockout of NKCC1 restricted in GnRH neurons in a reversible fashion using tetracycline controlled gene expression system. Female mice, which expressed KCC2 in GnRH neurons, showed no pregnancy and abnormal estrous cyclicity and abnormal ovary containing many small follicles. These results suggest that the excitatory action of GABA on GnRH neurons has an important role in the female reproduction.