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Cortical feedback and olfactory processing

皮质反馈和嗅觉处理

基本信息

批准号：
10355509
负责人：
VENKATESH N MURTHY
金额：
$ 35.91万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10355509
关键词：
Aging Animals Architecture Area Axon Behavior Behavioral Behavioral Assay Brain Cells Classification Clutterings Code Complex Data Detection Discrimination Environment Feedback Food Foundations Goals Image Impairment Individual Interneurons Knowledge Lateral Learning Light Mammals Measures Mental disorders Methods Mus Nervous system structure Neurons Neurosciences Nose Odors Olfactory Cortex Olfactory Pathways Output Partner in relationship Pattern Performance Physiological Population Process Reporting Research Role Sensory Signal Transduction Smell Perception Specificity Stimulus Testing Training awake calcium indicator efficacious treatment experience experimental study information processing interest mouse model multiphoton microscopy nervous system disorder novel olfactory bulb olfactory sensory neurons optogenetics recruit relating to nervous system response selective expression sensory neuroscience sensory stimulus sensory system tool

项目摘要

A key problem in sensory neuroscience is how nervous systems can detect objects of interest in noisy and cluttered sensory scenes, which then guide further action. This ability to pick out important information from the array of mixed stimuli is thought to involve extensive top-down modulation that interacts with feedforward processing of information. We propose to investigate this important function in the olfactory system of behaving mice using optogenetic and optophysiological methods. Olfaction is critical for the survival of many animals, which use this sense for to find food and mates, and to avoid predators. Information about volatile odorants sensed by olfactory sensory neurons is passed on to the olfactory bulb (OB), whose output reaches many cortical directly areas. This feedforward architecture is disrupted by massive feedback connections throughout the olfactory system, which are thought to provide context and learning-related signals to aid in odor perception. We recently developed an odor-guided behavioral task in which mice are required to parse complex odorous stimuli. In this project, we will use this exciting new behavioral assay to examine the role of cortical feedback to the OB in the genetically-accessible mouse model. To achieve our goals, we will first characterize how complex odor mixtures are represented in the OB, and then examine the effects of selective optogenetic perturbation of cortical feedback projections on the coding of complex odor stimuli in the OB. Then using a suite of cutting-edge methods already established in our group, we will uncover how the feedback signals conveyed to the OB evolve as mice learn to perform this task. Experiments in this project will be guided by three Aims. Aim 1: To determine how the output neurons of the OB represent odorant mixtures and how they are altered after mice learn the mixture task. Aim 2: To determine the effects of selective optogenetic perturbation of olfactory cortical neuron activity on odor coding in OB output neurons. Aim 3: To determine the features of stimulus-related signals carried by cortical feedback axons to the OB in naïve mice and in mice that have learnt the mixture task. The research proposed has broad relevance for neuroscience because it will shed light on how brains interpret ambiguous sensory stimuli in cluttered environments, an ability that is thought to involve top-down feedback. This ability is thought to be impaired with aging, as well as in some mental disorders. Therefore, understanding this process in the normal brain could help devise specific and efficacious treatments in abnormal conditions.

感觉神经科学中的一个关键问题是神经系统如何在嘈杂和嘈杂的环境中检测感兴趣的物体。杂乱的感官场景，然后引导进一步的行动。这种能力可以从混合刺激的阵列被认为涉及广泛的自上而下的调制，信息的前馈处理。我们建议调查这一重要功能的嗅觉使用光遗传学和光生理学方法的行为小鼠系统。嗅觉对于许多动物的生存，使用这种感觉来寻找食物和配偶，并避免捕食者。嗅觉神经元感知到的挥发性气味的信息传递给嗅球 (OB)其输出直接到达皮层的许多区域。这种前馈结构被以下因素破坏：整个嗅觉系统中的大量反馈连接，被认为提供了上下文，学习相关的信号来帮助气味感知。我们最近开发了一种气味引导的行为任务，哪些老鼠需要解析复杂的气味刺激。在这个项目中，我们将使用这个令人兴奋的新行为分析，以检查在遗传可接近小鼠中对OB的皮质反馈的作用模型为了实现我们的目标，我们将首先描述复杂的气味混合物在 OB，然后检查皮质反馈投射的选择性光遗传学扰动对 OB中复杂气味刺激的编码。然后使用一套先进的方法建立在我们的小组，我们将揭示如何反馈信号传递到OB演变为小鼠学会执行这项任务。本项目的实验将遵循三个目标。目标1：确定 OB的输出神经元是如何代表气味混合物的，以及在小鼠学习后它们是如何改变的。混合任务目的2：探讨选择性光遗传学微扰对嗅皮层的影响嗅球输出神经元中气味编码的神经元活动。目的3：确定刺激相关的特征在未处理的小鼠和已经学习混合物的小鼠中，由皮层反馈轴突携带到OB的信号任务这项研究对神经科学有着广泛的意义，因为它将揭示大脑是如何在混乱的环境中解释模糊的感官刺激，这种能力被认为涉及自上而下反馈这种能力被认为会随着年龄的增长而受损，以及在一些精神疾病中。因此，我们认为，了解正常大脑中的这一过程可以帮助设计出具体有效的治疗方法，异常情况