Neuron-type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct

Abstract

Cortical electrical stimulation (CNM) is widely used to promote recovery after stroke. Despite beneficial results, current CNM techniques are unable to differentiate the roles played by different neuron types in their effects. Our aim was to use selective optogenetic cortical stimulation to explore how different subpopulations of neuronal cells contribute to post-stroke recovery. We transduced sensory-parietal cortex (SPC) in rats with CamKII-ChR2 (pyramidal neurons), PV-ChR2 (parvalbumin-expressing inhibitory neurons), or hSyn-ChR2 (pan-neuronal population) before inducing photothrombotic capsular infarct lesions. We found that selective stimulation of inhibitory neurons produced significantly greater motor recovery than stimulation of excitatory neurons or the pan-neuronal population. Furthermore, 2-deoxy-2-[18F] fluoro-D-glucose microPET (FDG-microPET) imaging revealed the significant reduction of cortical diaschisis and activation of corticostriatal neural circuit, which were correlated with behavioral recovery in the PV-ChR2 group. The spatial pattern of brain-derived neurotrophic factor (BDNF) expression was evident in stimulated cortex and underlying cortico-subcortical circuit. Our results indicate that plasticity of inhibitory neurons is crucial for functional recovery after capsular infarct. Modifying CNM parameters to potentiate the stimulation of inhibitory neurons could enhance post-stroke outcomes.