GABA EFFECTS ON GNRH NEURONAL MIGRATION

促性腺激素释放激素（GnRH）神经元的正常功能 是生物体繁殖成功的必要条件期间 在发育过程中，GnRH神经元的迁移路线从它们的 外周发源地在嗅基板，穿过筛状 板和其最终目的地在基底前脑（BF）。 这些 神经元沿着嗅觉纤维迁移。这些纤维的断裂 会导致嗅觉丧失和性腺功能减退 的机制 导致这种相对独特的迁移的原因在很大程度上是未知的。 初步数据显示神经递质γ-氨基丁酸 谷氨酸（GABA）可能在调节GnRH神经元迁移中起作用。 我们 开发了一种切片制备方法， GnRH迁移途径。 目前的建议侧重于3个具体的 这是GABA效应的一部分。 第一，三人的参与 特异性GABA受体将通过定位研究， 这些受体沿着迁移路线，通过使用免疫细胞化学 并通过体外胚胎切片中的特异性受体激活。 第二，Ca ~（2+）在GABA介导的GnRH神经元迁移中的作用， 通过使用Ca 2+通道阻滞剂和Ca 2 + 螯合剂以及GABA能药物。 第三，存在 GABA在GnRH神经元亚群中的作用将在两个 的方式 首先，在这些GnRH神经元中发现GABA的过程 将通过免疫细胞化学方法对合成酶进行探索 谷氨酸脱羧酶（GAD 65和GAD 67）或醛 脱氢酶（AD）和GABA转运蛋白GAT-1。 二、作用 在GABA介导的GnRH神经元迁移中， 通过使用GAD和AD抑制剂以及GAT阻断剂进行研究 此外，在体外GABA能药物。

The proper functioning of gonadotropin releasing hormone (GnRH) neurons is necessary for the reproductive success of an organism. During development, the migratory route of GnRH neurons proceeds from their peripheral birthplace in the olfactory placode, across the cribriform plate and to their final destination in the basal forebrain (BF). These neurons migrate along olfactory fibers. The disruption of these fibers during development results in anosmia. and hypogonadism. The mechanisms that contribute to this relatively unique migration are largely unknown. Preliminary data suggest that the neurotransmitter gamma-aminobutyric acid (GABA) may play a role in regulating GnRH neuronal migration. We have developed a slice preparation which maintains the integrity of the GnRH migratory pathway. The current proposal focuses on 3 specific aspects of this GABA effect. First, the involvement of the three specific GABA receptors will be investigated through localization of these receptors along the migratory route by use of immunocytochemistry and through specific receptor activation in embryonic slices in vitro. Second, the role of Ca2+ in GABA-mediated GnRH neuronal migration will be investigated through the use of Ca2+ channel blockers and Ca2+ chelators in addition to GABAergic drugs in vitro. Third, the presence of GABA in a subpopulation of GnRH neurons will be investigated in two ways. First, the process by which GABA is found in these GnRH neurons will be explored by immunocytochemistry for the synthesizing enzymes glutamic acid decarboxylase (GAD 65 and GAD 67) or aldehyde dehydrogenase (AD) and the GABA transporter, GAT-1. Second, the role of GABA in GnRH neurons in GABA-mediated GnRH neuronal migration will be studied through the use of GAD and AD inhibitors, and GAT blockers in addition to GABAergic drugs in vitro.