Thalamic Control of Cortical Sensory Processing During Active Sensing

项目摘要 我们的大多数感觉伴随着运动导向的行为，因为我们触摸，扫描，并与我们的互动。 环境这种感觉运动整合在躯体感觉中最为明显， 在主动感觉（例如手指在表面上摩擦）期间感觉到对纹理的感知。然而，在这方面， 目前还不清楚，即使是基本的感觉丘脑皮层回路如何控制自我产生的运动和活动， 感觉。特别是，丘脑功能障碍与许多神经感觉运动障碍有关 包括亨廷顿氏病、帕金森氏病和原发性震颤。为此提出的工作 因此，这项研究意义重大，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，为了产生非病理性丘脑皮层感觉的更好框架， 处理.本项目将具体确定小鼠丘脑神经系须核 （后内侧或POm）调节初级感觉皮层中正在进行的感觉信号（Aim 1）， 主动感知任务期间的感知可检测性（目标2）。由于运动和感觉输入， 丘脑腹系核可能对主动感觉中的基本感觉运动整合至关重要。这项工作 将是创新的，因为它将检查作为一个感官门，同时结合 群体皮层记录和操作丘脑皮层回路的新方法 行为这个项目将使用特定的基因工程小鼠来靶向光敏蛋白通道 沉默和驱动正在进行的丘系丘脑活动，同时提供感官输入， 胡须这项工作的中心假设是，丘脑神经系系统是一个感觉门 控制下游皮层过程的激活和刺激信息的可检测性 在积极的感觉。目标1将确定三种不同的丘脑系丘脑状态（对照， 使用局部场电位对感觉刺激的形状感觉皮层反应 电生理学和遗传编码电压指示器（Arclight）。目标2将决定行为 通过可逆性损害活动性和非活动性期间的神经系功能来研究神经系通路的相关性， 被动检测任务，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的框架，以在 丘脑功能障碍和复杂的神经系统疾病。该奖项将提供额外的资金， 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.