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发挥出色的作用。 执行这些任务的电路以及它们如何受经验影响的情况很差 明白了。我们最近的工作表明，早期产前经历会导致 气味诱发反应、回路连接和侧抑制的变化。 在这里，我们建议分析嗅球横向的依赖于经验的电路级变化 使用电生理学和光遗传学方法进行抑制。具体来说，我们将执行 旨在解决以下三个具体目标的实验和分析。 目标 1) 确定气味调节是否改变嗅球的固有特性 神经元。在大脑的许多部分，兴奋性输入增加的后果之一是减少 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 长期接触气味的动物的特定中间神经元类型也有所不同。 目标 2) 确定气味调节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 M72 激活后，对簇状细胞而非二尖瓣细胞的侧向抑制强度 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 改变。具体来说，我们将确定哪些突触或细胞负责这些 增强反应。 目标 3：确定气味调理如何影响气味诱发的反应。我们发表的 初步数据表明，长期接触会导致二尖瓣细胞气味广泛增加 诱发反应（通过麻醉动物体内 2-P 钙成像测量）。在这个 我们的目标是通过检查簇绒中气味诱发的反应来扩展这一观察结果 细胞，特别是在肾小球中被识别为接收输入的二尖瓣和簇状细胞中， 对条件气味做出反应。

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.