Seminar: "Dynamic Thalamocortical Circuit Mechanisms and Neuromodulation in Chronic Pain" - Lori Scarpa

Endocrinology and Animal Biosciences Seminar

Lori Scarpa
PhD Student
Graduate Program in Endocrinology and Animal Biosciences

This dissertation proposal will investigate how higher-order thalamocortical circuits are organized, recruited, and regulated during chronic neuropathic pain. Higher-order thalamic nuclei communicate with cortical regions involved in complementary dimensions of pain, including the anterior cingulate cortex (ACC) and insular cortex (InsCx), yet the contributions of these projection-defined pathways remain poorly understood. I will first use retrograde tracing and activity-dependent labeling to identify the thalamic populations that project to the ACC and InsCx, and determine which populations are recruited during chronic pain. Preliminary tracing demonstrates successful targeting of both cortical regions and consistent retrograde labeling within the central medial and anteromedial thalamic nuclei. Next, I will use longitudinal fiber photometry with automated behavioral testing to determine how the activity of ACC-projecting and InsCx-projecting thalamic pathways changes across the transition from acute injury to chronic pain. These experiments will relate pathway activity to spontaneous pain-related behaviors and mechanically evoked hypersensitization. Finally, I will examine whether altered norepinephrine signaling contributes to higher-order thalamic dysfunction and pain behavior using genetically encoded fluorescent sensors and pathway-targeted chemogenetic manipulation. Together, these studies will define how projection-specific thalamocortical circuits and neuromodulatory signaling contribute to the development and maintenance of chronic pain.