Mechanisms of synapse specificity

突触特异性的机制

• 批准号: 7848595
• 负责人: ANIRVAN GHOSH
• 金额: $ 1.02万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7848595
• 关键词: Autistic Disorder; Axon; Brain; Cell Communication; Cell surface; Cells; Cloning; Complex; Cues; Destinations; Development; Electrophysiology (science); Environment; Epilepsy; Genes; Goals; Grant; Hippocampus (Brain); Immunofluorescence Immunologic; In Vitro; Individual; Lead; Mediating; Mental Retardation; Modeling; Molecular and Cellular Biology; Neuraxis; Neurons; Physiological; Population; Presynaptic Terminals; Process; Research Project Grants; Schizophrenia; Screening procedure; Signal Transduction; Specificity; Surface; Synapses; Synaptic Potentials; System; Testing; United States National Institutes of Health; base; cDNA Library; cell type; dentate gyrus; expression cloning; hippocampal pyramidal neuron; in vitro Assay; nervous system disorder; neurodevelopment; postsynaptic; preference; presynaptic; research study; synaptogenesis; time use

DESCRIPTION (provided by applicant): When a growing axon reaches its final destination in the brain, it is surrounded by multiple cell types that form a dense axonal and dendritic network. Within this complex environment, synapses form with high precision between specific pre- and post-synaptic cells. If this precision is not maintained and synaptogenesis is disrupted between normal synaptic targets or enhanced between non-physiological targets, it can lead to neurological disorders such as epilepsy, autism, mental retardation, and schizophrenia. How a cell distinguishes between the myriad of potential synaptic partners largely remains a mystery in the vertebrate central nervous system. The focus of this proposal is to investigate the basis of synaptic specificity during neural development. The experiments outlined here investigate the hypothesis that neurons in the CNS can differentiate between potential postsynaptic targetes based on cell-cell interactions mediated by cell surface molecules. We will explore this hypothesis by examining the ability of hippocampal dentate gyrus (DG) to preferentially innervate CAS neurons (their appropriate target) in mixed cultures. The goals of this exploratory grant are : (1) to establish a hippocampal microculture system in which synapse preference can be studied and to assess synaptic specificity using immunofluorescence and paired recodings; (2) to develop an expression cloning strategy that can be used to identify molecules that confer synaptic specificity. These findings would then serve as a platform for launching a longer-term project directed at cloning and characterizing genes that contribute to synaptic specificity.

描述（由申请人提供）：当生长的轴突到达大脑中的最终目的地时，它被形成密集的轴突和树突网络的多种细胞类型所包围。在这个复杂的环境中，突触前和突触后细胞之间具有高精度的突触形成。如果未维持此精度，并且在正常的突触靶标之间破坏了突触发生或在非生理靶标之间增强，则可能导致神经系统疾病，例如癫痫，自闭症，智力低下和精神分裂症。细胞如何区分无数潜在的突触伴侣，这在很大程度上仍然是脊椎动物中枢神经系统中的一个谜。该提案的重点是研究神经发育过程中突触特异性的基础。这里概述的实验研究了CNS中的神经元可以根据细胞表面分子介导的细胞 - 细胞相互作用来区分潜在的突触后靶标的假设。我们将通过研究海马齿状回（DG）优先支配CAS神经元（其适当的靶标）的能力来探讨这一假设。该探索性授予的目标是：（1）建立一个海马微培养系统，在该系统中可以研究突触偏好并使用免疫荧光和配对的重新编码来评估突触特异性； （2）制定一种表达克隆策略，该策略可用于识别赋予突触特异性的分子。然后，这些发现将作为启动针对克隆和表征有助于突触特异性的基因的长期项目的平台。