MOLECULAR ANALYSIS OF NEURONAL PHENOTYPE IN HIPPOCAMPUS

目标是识别和表征生化参数， 区分海马结构内的神经元细胞类型。 的 选择海马作为细胞和区域特异性基因模型 由于其相对简单的解剖结构， 仅由几种主要的神经元细胞类型组成， 发育、电生理和神经递质的特征 特性. 我们将研究特定的表达的解剖分布， mRNA转录本既位于细胞的明确亚核组织内， 海马和关于它们在神经元中的潜在表达， 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中进行研究， 这些转录本在细胞迁移过程中从表达的转录本中积累， 只有在突触发生后才能发生 编码蛋白质的一级序列 将根据潜在的信号肽来确定和评估， 糖基化和蛋白水解裂解。 这些翻译后 修改，连同它们的神经解剖分布 表达，应提供重要线索，以具体的性质， proteins. 相信这些研究将有助于了解 海马功能的生化基础 实验诱导 损伤和临床研究已经将海马结构与 这些复杂的行为现象，如短信息的获取和处理 术语记忆和癫痫发作的传播。 例如是 潜在的动物模型，为某些形式的癫痫在人类，突变 小鼠品系“摇摇欲坠”，将检查模式的改变， 基因表达可能是由原发性缺陷引起的， 蓝斑去甲肾上腺素能轴突对小脑的神经支配 海马结构 因此，这些研究可能会导致未来 实验过程中特定基因产物的作用的检查 诱发癫痫发作

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.