Assessing the Stability of the Motor Networks Recruited During the Bimanual String-Pulling Task Throughout Stroke Recovery

Abstract

In the absence of treatment following strokes, both humans and model organisms demonstrate partial improvements in motor function. Several endogenous mechanisms, such as cortical reorganization, are hypothesized to cause this spontaneous biological recovery. Reorganization of the motor cortex occurs within a time sensitive period and involves both proximal and distal sites of the intact brain. Despite these advancements, whether the same or different cells are used in the reorganized cortex after stroke remains unknown. In order to identify the motor networks involved in recovery, our lab has begun using the inducible Arc-CreERᵀ²:Rosa-YFPᶠᐟᶠ mice. In conjunction with the bimanual string-pulling task, this inducible model allows for the labelling of active cells throughout stroke recovery; either pre, 2 days post-stroke (dps) and 2 weeks post-stroke (wps). Behavioural deficits on the string-pull task were observed at 2 dps and accompanied by a decrease in active cells in the ipsilesional secondary motor (M2) cortex of stroke mice. By 2 wps, stroke mice had partial recovery of motor function with no differences in active cells in the ipsilesional M2. Interestingly, ~40% of cell in the motor cortex of sham and stroke mice were activated more than once while performing the string-pull task until 2 wps. Deeplabcut kinematic analysis of the string-pull task was also unable to identify differences in motor performance between stroke and sham mice. In addition, irrelevant of stroke injuries, only 60% of cells co-expressed the pan-neuronal marker NeuN after surgeries. Together these findings suggest that 40% of cells are reactivated up to 2 weeks post-stroke during the performance of a motor task, despite the acute decreases in active cells in the ipsilesional M2 of stroke mice. DeepLabCut kinematic results also highlight the need to redefine kinematic outcomes to better assess the full spectrum of stroke deficits.