PRESYNAPTIC ROLES OF GROUP II MGLURS IN HIPPOCAMPUS

代谢性谷氨酸受体(MGluRs)是近年来发现的一个家族。 克隆的谷氨酸受体通过G蛋白偶联到不同的第二 信使系统或离子通道。MGluRs的激活有多种 对海马体结构的生理影响。八个亚型 的mGluRs已被克隆，并可分为三大类 组。最近的研究已经定义了许多生理作用 组I的mGluRs(mGluR1和mGluR5)和组III的mGluRs (mGluRs4、6、7和8)。然而，人们对此知之甚少 第二组mGluR(mGluR2和mGluR3)的具体作用。 初步数据显示，II组mGluRs的一种选择性激动剂 减少穿通径-齿状回突触的传递。我们 假设第二组mGluR作为自体受体在 外侧和内侧穿支路突触。我们提出了一系列 旨在确定定位和生理作用的研究 II组海马区mGluRs的表达。我们将生产 抗II组mGluRs抗体并用于免疫细胞化学 确定II组mGluRs突触定位的研究。我们 也将检验这样一种假设，即激活一种受体 药理特征与II组mGluRs一致 减少穿孔剂路径上的传输。最后，我们使用 生物物理技术来确定细胞机制 II组mGluR激动剂调节穿透通路的传递 突触。

Metabotropic glutamate receptors (mGluRs) are a family of recently cloned glutamate receptors coupled via G-proteins to various second messenger systems or ion channels. Activation of mGluRs has a variety of physiological effects in the hippocampal formation. Eight subtypes of mGluRs have been cloned and can be classified into three major groups. Recent studies have defined many of the physiological roles of the group I mGluRs (mGluR1 and mGluR5) and group III mGluRs (mGluRs4,6,7, and 8) in the hippocampus. However, less is known about the specific roles of the groups II mGluRs (mGluR2 and mGluR3). Preliminary data reveal that a selective agonist of group II mGluRs reduces transmission at the perforant path-dentate gyrus synapse. We hypothesize that group II mGluRs serve as autoreceptors at the lateral and medial perforant path synapses. We propose a series of studies aimed at determining the localization and physiological roles of group II mGluRs in the hippocampal formation. We will produce antibodies for group II mGluRs and use them for immunocytochemical studies to determine synaptic localization of group II mGluRs. We will also test the hypothesis that activation of a receptor with a pharmacological profile consistent with that of group II mGluRs reduces transmission at the perforant path. Finally, we use biophysical techniques to determine the cellular mechanism by which group II mGluR agonists modulate transmission at perforant path synapses.