Integrative mechanisms of mitral cells

拟议的研究旨在阐明整合机制。 嗅球二尖瓣细胞，特别是当它们与肾小球有关时 嗅球的模式分析。二尖瓣细胞的两个新性质， 膜电位双稳态和长时间去极化(LLD)是 生物物理和药理学测量的特定焦点，以确定 产生这两种电流的内在电流和突触机制 二尖瓣细胞的特性。一种新的小鼠早期切片制备方法 保留嗅觉神经元和嗅球之间联系的大脑 将被用来检验关于综合函数的特定假设 双稳态和LLD。电压钳位协议将用于表征 内源性和突触激活的激活和失活曲线 逆行刺激二尖瓣外侧区诱发的二尖瓣细胞电流 嗅束和顺序性刺激嗅神经。双人 二尖瓣细胞顶端树突和胞体的细胞内记录 建议从接收输入的两个二尖瓣细胞进行成对记录 同样的肾小球。互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同步 同一肾小球内的树突。还将使用双二尖瓣细胞记录 检验双稳态调节二尖瓣敏感性的假设 细胞对嗅神经的输入和作为外侧脑区时间放大器的功能 抑制力。大鼠嗅球切片制剂的研制 出生后小鼠可用DIC/IR显示二尖瓣细胞 光学，从而可以制造生物物理和整合突触机制 通常采用双细胞内记录。正常和转基因小鼠将被 用于解决二尖瓣细胞中神经递质受体作用的问题 综合机制。初步数据显示，建议的技术是 在皮？S实验室工作。

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.