Thalamic Control of Cortical Sensory Processing During Active Sensing

项目摘要 当我们触摸、扫描和与我们的计算机交互时，我们的大多数感觉伴随着运动控制的行为 环境。这种感觉运动的整合在躯体感觉中最为明显，我们的触觉 对质地的感知是在主动感觉过程中感受到的，比如手指在表面上摩擦。然而， 目前还不清楚丘脑皮质基本感觉回路是如何控制自身产生的运动和活动的 轰动一时。特别是，丘脑功能障碍与许多神经感觉运动障碍有关。 包括亨廷顿氏症、帕金森氏症和特发性震颤。为此提出的工作 因此，团契关系将是重要的，因为它将阐明特定的丘脑核团如何调节信息。 在主动感觉期间，以便产生更好的非病理性丘脑皮质感觉框架 正在处理。该项目将专门确定小鼠丘脑旁核须是如何形成的 (后内侧或POM)调节初级感觉皮质中正在进行的感觉信号(目标1)和 主动感知任务中的感觉可探测性(目标2)。由于运动和感官输入， 丘脑旁核对于主动感觉的基本感觉运动整合可能是至关重要的。这部作品 将是创新的，因为它将检查副大脑系统作为感觉门，同时结合 人群皮质记录的新方法和丘脑皮质环路的操作 行为。该项目将使用特定的基因工程小鼠来定位光敏蛋白通道。 沉默和驱动丘脑旁正在进行的活动，同时提供感觉输入到 胡须。这项工作的中心假设是丘脑旁系统是一个感觉门。 控制下游皮质突起的激活和刺激信息的可检测性 在活跃的感觉过程中。目标1将确定三种不同的丘脑旁核状态(对照， 使用局部场电位形成对感觉刺激的静音和主动)感觉皮质反应 电生理学和遗传编码的电压指示器(Arclight)。目标2将决定行为 可逆性损害大脑旁功能与大脑旁通路的相关性 被动探测任务的同时记录神经相关。这项工作的影响将是扩大目前的 丘脑皮质感觉运动整合框架，以开发更好的治疗方案 丘脑功能障碍和复杂的神经系统疾病。这项奖励将提供额外的资金和 这项拟议工作的成功所需的支持通过额外的实验、分析和 科学训练。

Project Summary Most of our sensations accompany motor directed behavior as we touch, scan, and interact with our environment. This sensorimotor integration is most apparent in somatosensation, where our tactile perceptions of texture are felt during active sensation, such as rubbing a finger across a surface. However, it is unclear how even basic sensory thalamocortical circuits control self -generated motion and active sensation. In particular, thalamic dysfunction has been linked to many neurological sensorimotor disorders including Huntington’s Disease, Parkinson’s Disease, and Essential Tremor. The work proposed for this fellowship will therefore be significant because it will elucidate how specific thalamic nuclei regulate information during active sensation in order to generate a better framework of non-pathological thalamocortical sensory processing. This project will specifically determine how the mouse paralemniscal whisker thalamic nucleus (Posterior Medial or POm) modulates ongoing sensory signals in the primary sensory cortex (Aim 1) and sensory detectability during an active sensing task (Aim 2). Due to both motor and sensory input, the paralemniscal thalamic nuclei may be vital for basic sensorimotor integration in active sensing. This work will be innovative because it will examine the paralemniscal system as a sensory gate while combining novel methods for population cortical recording and manipulation of the thalamocortical circuit during behavior. This project will use specific genetically engineered mice to target light sensitive protein channels to silence and to drive ongoing paralemniscal thalamic activity, while providing sensory input to the whiskers. The central hypothesis for this work is that the paralemniscal thalamic system is a sensory gate that controls the activation of downstream cortical processes and the detectability of stimulus information during active sensation. Aim 1 will determine how three different paralemniscal thalamic states (control, silenced, and active) shape sensory cortical response to sensory stimuli using local field potential electrophysiology and a genetically encoded voltage indicator (Arclight). Aim 2 will determine the behavioral relevance of the paralemniscal pathway by reversibly lesioning paralemniscal function during an active and passive detection task while recording neural correlates. The impact of this work will be to expand the current framework of thalamocortical sensorimotor integration to develop better treatment options during states of thalamic dysfunction and complex neurological disease. This award will provide the additional funding and support required for the success of this proposed work through additional experimental, analytical, and scientific training.