Cortical feedback modulation of sensory processing during selective detection

项目总结/摘要 心理健康的一个标志是能够根据情境灵活地与周围环境雅阁。 背景和内部目标。一个长期存在的皮质生理学理论认为， 处理是由皮层反馈通路介导的。根据这一理论，内部状态与 背景或目标方向在额顶叶皮层中编码。这些信号通过大脑皮层传播 沿着皮层反馈通路，由此他们设定影响表征的初始条件 和感官反应的路由。然而，皮质反馈功能的机械描述是 由于难以研究行为主体的特定皮层通路，因此受到限制。方式和领导方法的创新 建议来自于结合一个定义良好的模型系统，定量行为，和先进的遗传 和生理工具。我们研究了一个运动到感觉皮层反馈通路在小鼠胡须 系统我们的实验旨在验证运动皮层反馈如何影响感官的假设 大脑皮层处理传入的感官刺激。我们实现了一个定量的感官检测任务， 小鼠学会对目标刺激做出反应并忽略干扰刺激。因此，我们的建议将揭示 皮层反馈对目标刺激检测和非目标刺激（“噪声”）的贡献 镇压我们特别假设，运动到感觉皮层反馈改善任务 通过感觉皮层噪声抑制来减少非目标反应。我们研究这些 在行为、皮层反馈群体活动和感觉皮层单个单位的分辨率处理 感觉处理我们使用了一系列尖端的生理学工具，包括特定通路的皮质 反馈光遗传学抑制，轴突和终末的Ca 2+成像以及 识别神经元细胞类型。总之，这些研究将提供对大脑皮层的机械理解， 目标导向行为中的反馈信号。此外，这些研究将产生新的假设， 皮层反馈的干扰如何可能导致与上下文相关的处理功能障碍， 神经精神疾病。

Project Summary/Abstract A hallmark of mental health is the ability to flexibly interact with our surroundings accord to situational context and internal goals. A long-standing theory of cortical physiology is that context-dependent neural processing is mediated by cortical feedback pathways. According to this theory, internal states related to context or goal-direction are encoded in fronto-parietal cortices. These signals propagate throughout cortex along cortical feedback pathways, whereby they set the initial conditions that influence the representation and routing of sensory responses. Mechanistic descriptions of cortical feedback function, however, are limited due to the difficulty of studying specific cortical pathways in behaving subjects. Innovations in this proposal come from combining a well-defined model system, quantitative behavior, and advanced genetic and physiological tools. We study a motor-to-sensory cortical feedback pathway in the mouse whisker system. Our experiments are designed to test hypotheses for how motor cortex feedback informs sensory cortex about processing incoming sensory stimuli. We implement a quantitative sensory detection task, in which mice learn to respond to target stimuli and ignore distractor stimuli. Thus, our proposal will reveal cortical feedback contributions to both target stimulus detection and non-target stimulus (‘noise’) suppression. We specifically hypothesize that motor-to-sensory cortical feedback improves task performance by reducing non-target responses through sensory cortex noise suppression. We study these processes at the resolution of behavior, cortical feedback population activity and sensory cortex single unit sensory processing. We use a host of cutting-edge physiological tools including pathway-specific cortical feedback optogenetic suppression, Ca2+ imaging of axons and terminals and multielectrode recordings of identified neuronal cell-types. Together, these studies will provide mechanistic understandings of cortical feedback signaling during goal-directed behavior. Additionally, these studies will generate new hypotheses for how disturbances of cortical feedback may contribute to dysfunctions of context-dependent processing in neuropsychiatric disease.