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.