Assessing Motor Impairments in a Mouse Model of Perinatal Stroke Through Brain Mapping and Behaviour

Abstract

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.