Abstract
Stroke injury and incomplete long-term stroke recovery remain key health issues in the United States and world-wide. We seek to help identify cellular dysfunction of the motor cortex after stroke, and its possible circuit remodeling during stroke recovery, since this structure is heavily implicated in this biology. We propose to measure evoked motor responses during long-train intracortical microstimulation (LT-ICMS) of motor cortex in the mouse as a method to identify the functional organization of this structure and plasticity following experimental stroke that relates to functional recovery. This work is one of the first to use LT-ICMS in mice after experimental stroke and it is employed in this study because it evokes complex, multi-joint forelimb movements that may match the temporal activity patterns of motor cortical cells during volitional movement and relate to skilled motor behavior. Permanent stroke injury is induced here using photothrombotic occlusion of the distal middle cerebral artery (MCAo) using Rose Bengal dye and green laser photostimulation. Skilled motor behavior is tested using the single pellet reaching task. Each mouse completes 30 days of post-injury or sham-injury single pellet reaching that is followed by an evaluation of cortical forelimb movement representation using LT-ICMS and then histological testing of lesion size and location. LT-ICMS is delivered as 500 millisecond trains of biphasic 200 microsecond pulses (delivered at 333 Hz) via a platinum/iridium microelectrode. The microelectrode is applied to test sites across the motor cortex (354 micron spacing) that are each at a depth of 800 microns. Evoked movements to LT-ICMS are quantified using high-speed video kinematic tracking of the forelimb. Experimental blind conditions are maintained until study completion. Statistics are then used to relate outcomes of behavioral reaching, LT-ICMS, and lesion characteristics. Collectively, the goal of this project is to understand whether (and how) complex movement representations derived by LT-ICMS change during stroke recovery in order to guide rehabilitative and interventional stroke therapies.
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