Cell-type-specific contributions of primary somatosensory cortex to skilled forelimb control - this project aims to uncover the circuit mechanisms by which the primary somatosensory cortex contributes…

The National Institute of Neurological Disorders and Stroke awarded Duke University $100,228 on December 16, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853, assistance type: Project Grant F31NS149497).

The project investigates cell-type-specific contributions of the primary somatosensory cortex to skilled forelimb control using two-photon calcium microscopy, optogenetic perturbation, genetic access to projection neuron types via mouse lines, naturalistic forelimb behavior paradigms, and computational analysis. The research aims to uncover circuit mechanisms by which the primary somatosensory cortex contributes to skilled forelimb behavior to inform future treatments for sensorimotor impairment in neurological conditions such as stroke, dystonia, and Parkinson's disease. The project tests the hypothesis that the upper limb primary somatosensory cortex implements sensorimotor control through two complementary strategies: intratelencephalic neurons relay voluntary behavior-related sensory signals to motor cortex via the corticocortical pathway to inform online motor control, while pyramidal tract neurons integrate both voluntary and passive sensory information to modulate afferent input via the corticofugal pathway.

Performance location is Durham, North Carolina. The period of performance runs through August 31, 2028.

Cell-type-specific contributions of primary somatosensory cortex to skilled forelimb control - this project aims to uncover the circuit mechanisms by which the primary somatosensory cortex contributes to skilled forelimb behavior to inform future treatments for sensorimotor impairment in neurological conditions such as stroke, dystonia, and parkinson's disease. Skilled forelimb behaviors such as reaching and grasping require not only motor execution but also real-time sensory feedback - including tactile signals that inform contact features and proprioceptive signals that encode limb position - to ensure precision and coordination. Sensory input from the body ascends to the primary somatosensory cortex (SSP), where IT is processed and relayed to downstream motor regions. Within SSP, distinct subtypes of projection neurons - intratelencephalic (IT) and pyramidal tract (PT) neurons - serve as the core circuit elements that route sensory information through corticocortical or corticofugal pathways. While this feedforward framework has shaped classical models of sensorimotor processing, the specific circuit-level mechanisms by which cell types contribute to skilled movement remain poorly understood. This project combines two-photon calcium microscopy, optogenetic perturbation, genetic access to projection neuron types via mouse lines, naturalistic forelimb behavior paradigm, and computational analysis to test the hypothesis: SSP-UL implements sensorimotor control via two complementary strategies: IT neurons relay voluntary behavior-related sensory signals to the motor cortex via the corticocortical pathway to inform online motor control, while PT neurons integrate both voluntary and passive sensory information to modulate afferent input via the corticofugal pathway. Aim 1 will define how IT and PT subtypes differentially encode proprioceptive and tactile input across active and passive contexts, revealing sensory processing logic of SSP-UL circuits. Aim 2 will determine the causal contributions of PN subtypes to skilled movement, linking cell-type-specific activity to sensory demanding features such as movement smoothness, body-part coordination, and fine motor control. Together, these studies will uncover the cell-type- specific encoding and functional roles of SSP-UL circuits, advancing fundamental models of cortical output and sensorimotor integration. By revealing how somatosensory signals are transformed into motor-relevant output at the circuit level, this work may inform new approaches to neuroprosthetic design and treatments for movement disorders with sensory-motor integration deficits. The applicant will receive advanced training in two-photon imaging, behavior assays, circuit manipulation, and computational neuroscience. Mentorship from DR. Huang and CO-sponsor DR. LI will provide an environment with rigorous guidance and training, access to necessary equipment, and professional development opportunities. To complement the scientific training, the applicant is also pursuing coursework in innovation and entrepreneurship, which provides exposure to translational pathways including neurotechnology development. Collectively, this project and training plan will establish a strong foundation for a successful career at the intersection of basic neuroscience and translational applications.