Experience-dependent plasticity of olfactory bulb circuits

项目摘要/摘要 嗅觉系统可以在识别和检测气味方面执行显著的任务。 执行这些任务的回路以及它们是如何受经验影响的都很差 明白了。我们最近的研究表明，早期的产前经验会导致 气味诱发反应、回路连通性和侧向抑制的变化。 在这里，我们建议分析经验依赖的嗅球外侧电路层的变化。 使用电生理和光遗传方法进行抑制。具体地说，我们将表演 实验和分析旨在解决以下三个具体目标。 目的1)确定气味调节是否改变嗅球的固有特性 神经元。在大脑的许多部位，兴奋性输入增加的一个后果是减少 主神经元的兴奋性。我们将测试二尖瓣和/或簇生细胞的兴奋性 以及特定的中间神经元类型在长期气味暴露的动物中是不同的。 目的2)确定气味条件作用如何改变嗅球的突触特性 电路。我们的初步数据表明，暴露于M72配体会增加 激活M72后对簇生的二尖瓣细胞的侧向抑制强度，但不包括二尖瓣细胞 肾小球。我们将通过确定塑料的回路机制来评估这种可塑性 变化。具体地说，我们将确定哪些突触或细胞负责这些 增强了响应能力。 目的3：确定气味条件作用如何影响气味诱发反应。我们出版的 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 目的我们建议通过检测丛生植物的气味诱发反应来扩展这一观察结果。 细胞，特别是二尖瓣和簇生细胞，被鉴定为接受肾小球的输入， 对条件性气味做出反应。

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.