Abstract TMP35: Optogenetic Stimulation Of Motor Cortex Neurons Promotes Recovery After Stroke

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Objective: Functional recovery after stroke has been observed in both animal and human studies and is currently attributed to both brain remodeling and plasticity. Brain stimulation techniques such as electrical stimulation and transcranial magnetic stimulation have been used successfully to enhance recovery. However, what mediates this recovery is not well understood. Elucidating the mechanism(s) is difficult because these stimulation techniques non-specifically activate all cell types near the stimulation site. Here we use optogenetic techniques to specifically stimulate layer V pyramidal neurons in the ipsilesional motor cortex at day 5 post-stroke, and investigate the effects on functional recovery as well as underlying mechanisms. Methods: Thy-1-ChR2-YFP line-18 transgenic male mice were used. Mice underwent stereotaxic surgery to implant a fiber cannula in the ipsilesional M1. All mice were then subjected to an intraluminal middle cerebral artery suture occlusion (30min). Optogenetic stimulation began at day 5 post-stroke and continued until day 14 post-stroke. Sensorimotor behavior tests were used to assess their behavioral recovery at day 0, 2, 7, 10 and 14 post-stroke. Body weights were also measured. Changes in cerebral blood flow were measured at day 14 post-stroke using the Laser Doppler Flowmetry. Results: Rotating beam test revealed that stimulated mice recovered significantly faster than non-stimulated control mice at day 10 and 14 after stroke (p<0.05). Stimulated mice also performed significantly better in the adhesive tape test at day 14, with a shorter tape removal time on the contralesional limb (p<0.05). Additionally, a significantly faster regain of body weight was observed in stimulated mice after stroke (p<0.05-0.01). Cerebral blood flow measurements revealed that stimulated mice exhibited significantly larger increase in cerebral blood flow at day 14 post-stroke (p<0.05-0.01). Conclusion: These data indicate that optogenetic stimulation of motor cortex neurons can promote behavioral recovery in mice after stroke. Current studies examine the mechanisms underlying this recovery, including genes related to neurovascular coupling and neurotrophic factors after stimulation.