Thursday, November 21, 2024
11/21/2024
Unilateral amputation, nerve damage or stroke cause widespread and robust changes in neural activity revealed in patient imaging studies. Successful rehabilitation of affected limbs after stroke, spared senses or intact limbs after nerve injury, or incorporation of prosthetics in an amputee’s daily life relies on the brain’s ability to adapt to these changes. On the other hand, chronic pain conditions such as phantom limb pain, hyperalgesia or complex regional pain syndrome are also proposed to be a result of cortical rewiring following some of these perturbations. The mechanisms underlying these phenotypes are unknown. We have developed an animal model which displays remarkably similar neural activity phenotypes during functional magnetic resonance imaging (fMRI). I have characterized the synaptic basis of the interhemispheric plasticity that is thought to underlie either adaptive or maladaptive plasticity in patients. The goal of the K99/R00 project is to characterize the specific neurons and synapses in the cortical circuit and determine if the changes we observe have a functional output to mediate more widespread changes in the brain. The functional relevance of these changes in connectivity will help determine if the plasticity we observe is adaptive, maladaptive or both. During the K99 training phase I will use a combination of fMRI, slice electrophysiology, viral tracing, and single nucleus RNA sequencing to identify key players that mediate these changes in neural activity. These results will guide experiments in the R00 phase, where I will modulate these cells with targeted interventions to re-calibrate the system. I will also use behavior to determine if the interventions are functionally relevant in vivo. The identification of specific subsets of neurons and their functional output will enable characterization of cortical rewiring after peripheral nerve injury. I will determine which neurons may be underlying adaptive or maladaptive plasticity. By targeting these neurons for therapeutic purposes, I will enhance adaptive plasticity to mediate better recovery or reduce pain conditions caused by maladaptive plasticity. These interventions may be clinically beneficial, but in order to be most effective complete characterization of the circuit underlying these changes is required.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
