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

Abstract

Cortical neuromodulation (CNM) is widely used to promote recovery after stroke. Despite the beneficial results of CNM, the roles played by different neuron types in the effects of current CNM techniques are unable to be differentiated. Our aim was to use selective optogenetic cortical stimulation to explore how different subpopulations of neuronal cells contribute to poststroke recovery. We transduced the sensory-parietal cortex (SPC) of 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 resulted in 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 a significant reduction in cortical diaschisis and activation of the 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 the stimulated cortex and underlying cortico-subcortical circuit. Our results indicate that the plasticity of inhibitory neurons is crucial for functional recovery after capsular infarct. Modifying CNM parameters to potentiate the stimulation of inhibitory neurons could improve poststroke outcomes.

Inhibitory neuron plasticity key to functional recovery post-stroke

Stroke, a major cause of long-term disability, has few treatment options. This research explores cortical neuromodulation, a method that changes brain activity, to improve motor functions and life quality for stroke patients. The study used optogenetic technology, which enables accurate stimulation of specific neuron types, to see how different neurons aid recovery after a stroke. They discovered that stimulating a particular neuron type, parvalbumin-expressing neurons, led to the most recovery. The research involved 8-week-old male rats, divided into three groups: control, sham, and optogenetic stimulation. They used a method called single pellet reaching task (SPRT) to assess the rats’ recovery after a stroke. The results showed that the group with optogenetic stimulation of parvalbumin-expressing neurons recovered the most. Moreover, they found that recovery circuit activation depends on the specific neurons stimulated.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.