UCLA

Stroke is a leading cause of disability and there is a need for therapies which enhance the spontaneous amount of brain recovery that occurs naturally. PDE2a is a promising molecular target which may limit recovery. Here, two-photon calcium imaging is employed to study the primary motor cortex (M1) and the premotor cortex (M2) of mice before and after inducing a PT stroke to M1. Mice received daily PDE2a-inhibitor as a recovery agent after stroke, and were imaged weekly for 5 weeks. Head-fixed behavior was concurrently assessed during spontaneous and forced-use contexts. Calcium recordings were processed and analyzed, and functional connectivity (FC) was assessed based on the correlatedness of the neurons in the recording. Stroke was found to have significant negative effects on FC, especially in M1. Stroke had differential effects in M2 during Spontaneous behavior vs forced use behavior. Finally, PDE2a-inhibition shows a strong trend for improving head-fixed recovery after stroke and it is a significantly positive enhancer of FC in M1 and M2. The results suggest that calcium imaging can act as a biomarker for stroke and that PDE2a-inhibition is an ideal molecular target.