Integrative mechanisms of mitral cells

二尖瓣细胞的整合机制

• 批准号: 6597579
• 负责人: Michael Thomas Shipley
• 金额: $ 22.85万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6597579
• 关键词: cellular polarity; genetically modified animals; laboratory mouse; membrane potentials; olfactions; olfactory lobe; tissue /cell preparation; voltage /patch clamp

The proposed research aims to elucidate the integrative mechanisms of olfactory bulb mitral cells, particularly as they relate to glomerular pattern analysis in the olfactory bulb. Two novel properties of mitral cells, membrane potential bistability and long lasting depolarizations (LLDs), are the specific focus of biophysical and pharmacological measurements to determine the underlying intrinsic currents and synaptic mechanisms producing these two properties of mitral cells. A novel slice preparation of early postnatal mouse brain which retains connections between olfactory neurons and olfactory bulb will be used to test specific hypotheses concerning the integrative functions of bistability and LLDs. Voltage clamp protocols will be used to characterize the activation and inactivation curves of intrinsic and synaptically activated currents in mitral cells elicited by antidromic stimulation of the lateral olfactory tract and orthodromic stimulation of the olfactory nerve. Dual intracellular recordings from the apical dendrite and soma of a mitral cell are proposed as are pairwise recordings from two mitral cells receiving input from the same glomerulus. Cross correlation techniques will be applied to test whether LLDs lead to synchronization of the mitral cell population with apical dendrites in the same glomerulus. Dual mitral cell recordings will also be used to test the hypothesis that bistability regulates the sensitivity of mitral cells to olfactory nerve inputs and functions as a temporal amplifier of lateral inhibition. The development of a viable olfactory bulb slice preparation from postnatal mouse makes possible the visualization of mitral cells with DIC/IR optics so that biophysical and integrative synaptic mechanisms can be made routinely with dual intracellular recordings. Normal and transgenic mice will be used to address questions of neurotransmitter receptor roles in mitral cell integrative mechanisms. Preliminary data show that the proposed techniques are working in the PI?s laboratory.

这项研究旨在阐明整合机制 嗅球僧帽细胞，特别是当它们与肾小球 嗅球的模式分析二尖瓣细胞的两个新特性， 膜电位双稳态和长持续去极化（LLDs）是 生物物理学和药理学测量的具体重点，以确定 产生这两种电流的潜在内在电流和突触机制 二尖瓣细胞的特性。一种新型小鼠生后早期切片制剂 保留嗅觉神经元和嗅球之间联系的大脑 将被用来测试有关的综合功能的具体假设， 双稳态和LLDs。电压钳协议将用于表征 内源性和突触激活的激活和失活曲线 外侧部逆行刺激引起的二尖瓣细胞电流 嗅束和嗅神经的顺向刺激。双 从二尖瓣细胞的顶端树突和索马的细胞内记录是 提出了从两个二尖瓣细胞接收输入的成对记录， 相同的肾小球。交叉相关技术将被应用于测试 LLD是否导致二尖瓣细胞群与心尖细胞群的同步化 树突在同一肾小球内。还将使用双二尖瓣细胞记录 为了验证双稳态调节二尖瓣敏感性的假设， 细胞的嗅觉神经输入和功能作为一个横向的时间放大器 抑制作用嗅球切片的研制 出生后的小鼠使DIC/IR显示二尖瓣细胞成为可能 光学，以便生物物理和整合突触机制， 常规地进行双重细胞内记录。正常和转基因小鼠将 用于解决二尖瓣细胞中神经递质受体作用的问题 整合机制初步数据显示，所提出的技术是 在PI工作？的实验室。