MECHANISMS OF DEPRESSION OF SYNAPTIC STRENGTH

突触强度抑制机制

• 批准号: 2698807
• 负责人: YUKIKO GODA
• 金额: $ 18.1万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2698807
• 关键词: developmental neurobiology; hippocampus; laboratory mouse; membrane potentials; neural inhibition; neural plasticity; neural transmission; neurophysiology; synapses; tissue /cell culture

DESCRIPTION (Adapted from applicant's abstract): The long-term objective is to delineate the basic principles governing synaptic connectivity in central neurons and the significance of these mechanisms to information storage as well as brain dysfunction underlying mental illnesses. Dissociated hippocampal neurons form functional synapses when grown in culture. Electrophysiological and imaging methods will be applied to investigate the cellular and molecular mechanisms of long-term depression (LTD) of synaptic strengths and the maintenance of the relative balance of synaptic inputs in simple circuits formed by cultured hippocampal neurons. I. Mechanisms of LTD in simple circuits: Culture preparation can provide answers to mechanisms of synaptic connectivity that cannot be addressed in brain slices. The first aim is to demonstrate the significance of LTD in culture by establishing its stability, pharmacological requirements, and the presynaptic mechanisms of LTD. II. Properties of LTD expression at individual synapses in simple circuits: The neuronal culture preparation will be fully exploited by using the activity-dependent fluorescent synapse marker FM1-43 to study LTD at the level of individual synapses. In particular, the spatial pattern of LTD expression and structural correlates of LTD at individual synapses will be characterized. III. Mechanisms regulating synaptic strengths in two cell circuit: Again, making use of the culture preparation, the regulation of relative strengths of synaptic inputs will be addressed. Specifically, the origin and the underlying mechanism leading to asymmetric synaptic inputs in reciprocally interconnected pairs of cultured hippocamal neurons will be studied.

描述（根据申请人的摘要改编）：长期目标是 描述中央的突触连接的基本原理 神经元和这些机制对信息存储的重要性 以及大脑功能障碍的精神疾病。 解离 海马神经元在培养中生长时形成功能突触。 电生理和成像方法将用于研究 长期抑郁（LTD）突触的细胞和分子机制 优势和维持突触输入的相对平衡 由培养的海马神经元形成的简单电路。 I.简单电路中有限公司的机制：文化准备可以提供 无法解决突触连通性机制的答案 脑切片。 第一个目的是证明Ltd在 通过建立其稳定性，药理要求和 Ltd的突触前机制。 ii。 LTD表达在简单电路中单个突触中的特性： 神经元文化的准备将通过使用 活动依赖性荧光突触标记FM1-43在研究LTD 单个突触的水平。 特别是Ltd的空间模式 LTD在单个突触时的表达和结构相关性将是 特征。 iii。 调节两个细胞电路突触强度的机制：再次 利用文化准备，相对优势的调节 突触输入将被解决。 具体而言，起源和 基本机制，导致反之表的不对称突触输入 将研究成对的培养的海马神经元对。