Perinatal stroke, which occurs before or shortly after birth, may result in both beneficial and maladaptive plasticity in surviving tissue. However, current preclinical and clinical work have an unclear understanding on the relationship between functional outcome and neurophysiology. This thesis aims to dually characterize and correlate behaviour with cortical motor representations in a mouse model of perinatal stroke. On postnatal day 7, a unilateral photothrombotic stroke was produced in the primary motor cortex of Thy1-ChR2 mice. Sensorimotor function was evaluated in adulthood with a battery of behavioural tests. Subsequently, a transcranial window was implanted, and motor maps were created through optogenetic point stimulation. To evaluate the impact of skilled motor training on cortical reorganization, mapping was conducted before and after training on the single pellet reaching task. P7 stroke caused functional impairments across a battery of motor tasks, while both motor map size and movement latency were bilaterally impacted. Spontaneous limb use was positively correlated with map size of both hemispheres, but single pellet performance was only positively correlated with map size in the injured hemisphere. Following skilled motor training, both map size reductions and delayed latency was partially restored. Additionally, significant correlations between map size expansion and movement latency reduction following skilled motor training not only demonstrate that training-induced plasticity was beneficial, but also primarily mediated by the uninjured hemisphere. As the first study to conduct within-animal optogenetic motor mapping following perinatal stroke, we show that 1) perinatal stroke bilaterally impacts both cortical and descending aspects of the motor system, 2) the remaining movement sites in both the uninjured and injured hemispheres have a positive impact on functional outcome, and 3) skilled forelimb training can partially restore cortical and descending motor neurophysiology.

Following a stroke, normal usage of the impaired limb guides spontaneous recovery across many months or even years; however, recovery is rarely complete. Pre-clinical tools are needed to investigate stroke-induced cortical reorganization over long periods. This thesis aims to characterize stroke impairment and spontaneous recovery in parallel with a battery of behaviour tasks in a mouse model of focal stroke. Young adult Thy1-ChR2 mice were implanted with a transcranial window over the intact skull permitting cortex visualization and enabling longitudinal assessments with light-based motor mapping and intrinsic signal optical imaging. Furthermore, mice were tested on sensorimotor behavioural tasks in parallel to the mapping experiments. These experiments allowed for the quantification of impairments in the sensorimotor cortex and forelimb function while identifying regions within the sensorimotor cortex that show re-mapping associated with behavioural recovery. Following primary motor cortex-stroke induction, both sensory and motor map impairments occurred. Sensory map transient impairments recovered within the same atlas-defined regions two weeks after a primary motor cortex stroke as identified by intrinsic signal optical imaging. In contrast, motor forelimb recovery was observed four weeks after the stroke in the peri-infarct region, the supplemental motor cortex, and the contralesional motor cortex. This recovery was identified through a combination of analyses, including changes in the mapped area and the amplitude of evoked forelimb movements using light-based motor mapping. Behavioural recovery occurred four to six weeks post-stroke, depending on the sensitivity of the task in forelimb impairment. Additionally, the contralesional hemisphere and forelimb did not show impairment acutely but evoked forelimb amplitude was significantly increased by post-stroke week four for both forelimbs. As the first study to conduct within-animal longitudinal spontaneous recovery sensory and motor map experiments using bilateral forelimb and hemispheric representations, we show that 1) photothrombotic stroke impacts both forelimb representations pertained within the ipsilesional hemisphere in LBMM experiments, 2) recovery of the impaired forelimb occurs ipsilesionally and contralesionally and, 3) impairments from stroke observed through motor mapping are functionally relevant and precede behavioural recovery ranging from zero to two or more weeks depending on the motor cortex's involvement in the behavioural task.