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检测噪声中感兴趣的对象和混乱的感觉场景，然后引导进一步的动作。从中挑选重要信息的这种能力据认为，混合刺激的阵列涉及与与之相互作用的广泛自上调制调制信息处理。我们建议研究嗅觉中的这一重要功能使用光遗传学和光生理方法的行为小鼠系统。嗅觉对许多动物的生存，这些动物利用这种感觉可以找到食物和伴侣，并避免捕食者。有关嗅觉感觉神经元感测的挥发性气味的信息已传递给嗅球（OB），其输出直接到达许多皮质区域。这种前馈结构被破坏了整个嗅觉系统中的大量反馈连接，被认为提供背景和与学习相关的信号，以帮助气味感知。我们最近在需要哪些小鼠来解析复合有臭刺激的复合物。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一般可访问的小鼠对OB的皮质反馈的作用模型。为了实现我们的目标，我们将首先描述如何在 OB，然后检查皮质反馈项目的选择性光遗传学扰动对 OB中复杂的气味刺激的编码。然后已经使用一套尖端方法我们将在我们的小组中建立，我们将发现反馈信号是如何传达给OB演变的学会执行此任务。该项目的实验将以三个目标指导。目标1：确定 OB的输出神经元如何表示气味混合物以及它们在学习后如何改变它们混合任务。目标2：确定嗅觉皮质的选择性光遗传学扰动的影响 OB输出神经元中气味编码的神经元活性。目标3：确定与刺激有关的特征皮质反馈轴突在幼稚的小鼠和学习混合物的小鼠中携带的信号任务。拟议的研究对神经科学具有广泛的相关性，因为它将阐明大脑如何解释混乱环境中的模棱两可的感觉刺激，这种能力被认为涉及自上而下反馈。人们认为这种能力被衰老以及某些精神障碍受到损害。所以，在正常大脑中了解这一过程可以帮助设计特定而有效的治疗方法异常条件。