Experience-dependent plasticity of olfactory bulb circuits

项目概要/摘要 嗅觉系统在识别和检测气味方面可以执行出色的任务。 执行这些任务的电路以及它们如何受到经验的影响很差 明白我们最近的研究表明，早期的产前经历会导致 气味诱发反应，电路连接和侧抑制的变化。 在这里，我们建议分析经验依赖性电路水平的变化，在嗅球外侧 使用电生理学和光遗传学方法抑制。具体来说，我们将执行 实验和分析旨在解决以下三个具体目标。 目的1）确定气味条件化是否改变嗅球的内在特性 神经元在大脑的许多部分，兴奋性输入增加的一个后果是减少 主要神经元的兴奋性我们将测试二尖瓣和/或簇状细胞的兴奋性是否 以及特定的中间神经元类型在长期暴露于气味的动物中不同。 目的2）研究气味条件化对嗅球突触特性的影响 电路.我们的初步数据表明，暴露于M72配体增加了 M72激活后对簇状细胞而非二尖瓣细胞的侧抑制强度 肾小球我们将通过确定塑料的电路机制来评估这种可塑性。 变化具体来说，我们将确定哪些突触或细胞负责这些 增强响应。 目的3：确定气味条件化如何影响气味诱发反应。我们的出版 初步数据显示，长期接触会导致二尖瓣细胞气味的广泛增加， 诱发反应（通过麻醉动物体内2-P钙成像测量）。在这 目的我们建议扩大这一观察，通过检查气味诱发的反应，簇绒 细胞，特别是在二尖瓣和簇状细胞中，这些细胞被鉴定为在肾小球中接收输入， 对条件反射的气味作出反应。

Project Summary/Abstract The olfactory system can perform remarkable tasks in the identification and detection of odors. The circuits that perform these tasks and how they are influenced by experience are poorly understood. Our recent work has demonstrated that early prenatal experience results in changes in odor-evoked responses, circuit connectivity and lateral inhibition. Here we propose to analyze experience-dependent circuit-level changes in olfactory bulb lateral inhibition using electrophysiological and optogenetic approaches. Specifically, we will perform experiments and analysis designed to address the following three specific Aims. Aim 1) To determine if odor conditioning alters the intrinsic properties of olfactory bulb neurons. In many parts of the brain, one consequence of increased excitatory input is reduced excitability of principle neurons. We will test whether the excitability of mitral and/or tufted cells as well as particular interneuron types differs in animals subject to long-term odor exposure. Aim 2) To determine how odor conditioning changes synaptic properties in olfactory bulb circuits. Our preliminary data indicate that exposure to an M72 ligand increases the strength of lateral inhibition onto tufted, but not mitral cells following activation of the M72 glomerulus. We will evaluate this plasticity by determining the circuit mechanisms of plastic change. Specifically we will determine which synapses or cells are responsible for these enhanced responses. Aim 3: To determine how odor conditioning affects odor-evoked responses. Our published and preliminary data show that long term exposure causes a broad increase in mitral cell odor evoked responses (measured by in vivo 2-P calcium imaging in anesthetized animals). In this Aim we propose to expand on this observation by examining odor-evoked responses in tufted cells and specifically in mitral and tufted cells identified as receiving input in glomeruli that respond to the conditioned odor.