MOLECULAR ANALYSIS OF NEURONAL PHENOTYPE IN HIPPOCAMPUS

目标是识别和表征生物化学参数， 区分海马区内的神经细胞类型。这个 海马区被选为细胞和区域特异性基因的模型 表达，因为它的解剖组织相对简单， 只由几种主要的神经细胞类型组成，因为它 发育、电生理和神经递质特性良好 属性。 我们将研究特定基因表达的解剖分布。 在确定的亚核组织中的mRNA转录 海马区及其在脑内神经元的潜在表达 大脑的其他区域。表达的发展程序将 在正常和突变品系的小鼠身上进行研究，以区分 那些在细胞迁移过程中积累的转录本 只有在突触发生之后。编码蛋白质的一级序列 将根据潜在的信号肽进行确定和评估， 糖基化和蛋白水解性切割。这些翻译后版本 修饰，以及它们的神经解剖分布 表达，应该提供关于特定性质的重要线索 蛋白质。 相信这些研究将有助于理解 海马区功能的生化基础。实验诱导 损伤和临床研究已将海马区结构与 短时记忆的习得和加工等复杂行为现象 癫痫发作的长期记忆和传播。例如，一个 突变的人类某些形式癫痫的潜在动物模型 小鼠品系“摇摇欲坠”，将被检查其模式的变化。 可能由原发缺陷引起的基因表达 蓝斑去甲肾上腺素能轴突对下丘脑的超神经支配 海马体结构。因此，这些研究可能会在未来 特定基因产物在实验过程中的作用检验 诱发癫痫发作活动。

The goal is to identify and characterize biochemical parameters that distinguish neuronal cell types within the hippocampal formation. The hippocampus is chosen as a model for cellular and regional specific gene expression because of its relatively simple anatomical organization, consisting of only several major neuronal cell types and because of its well characterized developmental, electrophysiological and neurotransmitter properties. We will examine the anatomical distribution of the expression of specific mRNA transcripts both within the defined subnuclear organization of the hippocampus and with respect to their potential expression in neurons of other regions of the brain. The developmental program of expression will be investigated in both normal and mutant strains of mice to distinguish those transcripts accumulated during cell migration from those expressed only after synaptogenesis. The primary sequence of the encoded protein will be determined and evaluated in terms of potential signal peptides, glycosylation and proteolytic cleavage. These post-translational modifications, together with the neuroanatomical distribution of their expression, should provide important clues as to the nature of the specific proteins. It is believed that these studies will contribute to an understanding of the biochemical basis of hippocampal function. Experimentally induced lesion and clinical studies have associated the hippocampal formation with such complex behavioral phenomena as acquisition and processing of short term memory and propagation of epileptic seizures. For example, a potential animal model for certain forms of epilepsy in humans, the mutant mouse strain "tottering", will be examined for alterations in patterns of gene expression which may result from the primary defect of hyperinnervation by noradrenergic axons of the locus coeruleus to the hippocampal formation. These studies, therefore, could result in future examination of the role of specific gene products during experimentally induced seizure activity.