ESTROGEN AND NEUROTRANSMITTER SYSTEMS IN HIPPOCAMPUS

与学习和记忆相关的神经元可塑性， 癫痫样活动取决于两种活动的精确平衡， 海马中的主要神经递质系统：兴奋性 谷氨酸/天冬氨酸神经元和抑制性γ-氨基丁酸 （GABA）神经元。 本研究的目的是检验这一假设 雌二醇和孕酮影响认知过程， 通过与谷氨酸和/或GABA相互作用的癫痫发作活动 神经元或其受体系统。 Escherichia coli增加了 NMDA、GABAA和孕酮受体与树突棘和突触 在海马CA 1区形成。 1） 通过改变构象和结合特性直接作用于受体 2）通过增加基因的转录和合成 或3）对神经递质的释放， 影响受体结合。 为了评估雌二醇的影响 在谷氨酸和/或GABAA受体系统上，基因水平 NMDA和GABAA受体基因的表达将使用以下方法测定： 原位杂交组织化学 行动的地点和重要性 通过植入抗雌激素来评估突触传递 进入内嗅皮层，它有一个主要的投射到 海马或雌激素处理的大鼠的背侧海马， 测量NMDA和GABAA受体结合位点和mRNA水平。 的 抗雌激素植入物将阻断雌二醇的局部作用。 在 此外，雌二醇对神经递质合成的影响， 释放将被评估。 mRNA水平和酶活性 谷氨酸脱羧酶（GAD），GABA的合成酶， 作为GABA神经元活性大小的指标进行测量。 孕激素受体与谷氨酸脱羧酶的免疫细胞化学共定位 肽将进行，以确定是否存在的机制，为 孕酮对GAD基因表达的直接作用。 分化 作用于细胞内孕酮的孕酮的作用 受体从其代谢产物的作用，别孕烯醇酮，其作用 在GABAA受体处，动物将用别孕烯醇酮治疗。 如果别孕烯醇酮模拟孕酮对GAD基因的作用， 表达，那么孕酮作用于GABAA受体。 的 这些研究的结果将有助于我们了解 细胞机制的影响，雌二醇对某些 行为方面的学习和记忆以及癫痫样活动。

The neuronal plasticity associated with learning and memory and epileptiform activity depends on precise balances in the activity of two major neurotransmitter systems in the hippocampus: the excitatory glutamate/aspartate neurons and the inhibitory gamma-aminobutyric acid (GABA) neurons. The objective of this research is to test the hypothesis that estradiol and progesterone influence cognitive processes and epileptic seizure activity by interacting with the glutamate and/or GABA neurons or their receptor systems. Estradiol increases the density of NMDA, GABAA, and progesterone receptors and dendritic spines and synapse formation in the CA1 region of the hippocampus. Estradiol may act 1) directly at the receptor by changing conformation and binding properties of the protein, 2) at the gene by increasing transcription and synthesis of receptor subunits, or 3) on neurotransmitter release which in turn affects receptor binding. In order to assess the influence of estradiol on the glutamate and/or GABAA receptor systems, the levels of gene expression of NMDA and GABAA receptor genes will be determined using in situ hybridization histochemistry. The site of action and importance of synaptic transmission will be assessed by implantation of an antiestrogen into the entorhinal cortex, which has a major projection to the hippocampus or into the dorsal hippocampus of estradiol-treated rats and measuring NMDA and GABAA receptor binding sites and mRNA levels. The antiestrogen implants will block the local effects of estradiol. In addition, the effects of estradiol on neurotransmitter synthesis and release will be assessed. The levels of mRNA and the enzymatic activity of glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA, will be measured as an indicator of the magnitude of GABA neuronal activity. Immunocytochemical colocalization of progesterone receptor and GAD peptide will be done to determine whether the mechanism exists for the direct action of progesterone on GAD gene expression. To differentiate the action of progesterone which acts at the intracellular progesterone receptor from the actions of its metabolite, allopregnanolone, which acts at the GABAA receptor, animals will be treated with allopregnanolone. If allopregnanolone mimics the action of progesterone on GAD gene expression, then progesterone is acting at the GABAA receptor. The results of these studies will contribute to our understanding of the cellular mechanisms underlying the effects of estradiol on certain behavioral aspects of learning and memory and epileptiform activity.