Postsynaptic targets and local circuit effects of cortical feedback inputs to the

描述(申请人提供)：我们的嗅觉可以帮助我们保护自己免受变质食物、气体泄漏或烟雾等环境危害的影响，并为我们的日常生活提供丰富的背景。然而，大脑中嗅觉信息处理和编码的潜在机制尚不清楚。气味信息首先在嗅觉尖峰中编码 感觉神经元，然后在嗅球中突触。以前的研究已经证明，嗅球神经元的活动随经验和环境的变化而变化，这可能会使动物更好地编码特别显著的气味信息。在这些行为条件下，从嗅皮层到嗅球的皮质反馈投射可能会调节“自上而下”的嗅球活动。尽管它们对早期感觉加工有潜在的影响，但这些皮质反馈投射的目标和基本性质仍然在很大程度上仍不清楚。皮质反馈投射突触在哪里，以及它们如何影响二尖瓣/簇状细胞的活动，在本提案中，我们将使用光遗传学方法解决这些问题。通道视紫红质(ChR2)在嗅皮层第2/3层锥体细胞中的病毒表达将被用来选择性和急性地激活小鼠嗅球切片中的锥体细胞轴突。利用细胞贴附和全细胞膜片钳记录，我们将检测皮层反馈投射的突触后靶点的ChR2诱发的反应。本研究有两个具体目标：目标1：确定皮层反馈投射的突触后靶点；目标2：确定皮质反馈对二尖瓣和簇状细胞输出的影响。

DESCRIPTION (provided by applicant): Our sense of smell can help protect us from spoiled foods, environmental hazards such as gas leaks or smoke, and provide a rich background to our daily lives. However, the mechanisms underlying the processing and coding of olfactory information in the brain are unclear. Odor information is first encoded in the spiking of olfactory sensory neurons, which in turn synapse in the olfactory bulb. Previous studies have demonstrated experience and context dependent changes in the activity of olfactory bulbar neurons, which may allow animals to better encode particularly salient odor information. Cortical feedback projections from the olfactory cortex to the olfactory bulb are poised to mediate the "top-down" regulation of olfactory bulb activity during these behavioral conditions. Despite their potential impact on early sensory processing, the targets and basic properties of these cortical feedback projections still remain largely unknown. Where do cortical feedback projections synapse, and how to they affect the activity of mitral/tufted cells, the output neurons of the bulb In this proposal, we will address these questions using an optogenetic approach. Viral expression of channelrhodopsin (ChR2) in layer 2/3 pyramidal cells of olfactory cortex will be used to selectively and acutely activate pyramidal cell axons in mouse olfactory bulb slices. Using cell-attached and whole-cell patch clamp recording, we will examine ChR2 evoked responses in postsynaptic targets of cortical feedback projections. This study has 2 specific aims: Aim 1: Characterize the postsynaptic targets of cortical feedback projections and Aim 2: Determine the effects of cortical feedback on mitral and tufted cell output.