Thalamic Control of Cortical Sensory Processing During Active Sensing

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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.