Probing the impact of cholinergic circuits in functional recovery after focal cerebral ischemia

The current thesis investigated the role of acetylcholine in recovery from diaschisis and skilled hand movement following ischemic stroke in a mouse model of photothrombotic stroke. Mice were trained in skilled reaching task in which they were taught to use their hand to reach for, grasp, and eat a food pellet. They were implanted with a fiber optic in their nucleus basalis, the main source of cholinergic projections to the sensorimotor cortex, for optogenetic stimulation and an electrode in their motor cortex for local field potential recordings. Then they received photothrombotic stroke in their primary forelimb somatosensory cortex. The general findings are that upregulation of acetylcholine reduced diaschisis following photothrombotic stroke to primary forelimb somatosensory area as measured by endpoint scores. However, upregulation of acetylcholine did not improve skilled hand movements as measured by movement component scores and fictive eating analysis.Canadian Institute of Health Research (CIHR

Information-theory analysis of mouse string-pulling agrees with Fitts\u27s Law: Increasing task difficulty engages multiple sensorimotor modalities in a dual oscillator behavior.

Mouse string pulling, in which a mouse reels in a string with hand-over-hand movements, can provide insights into skilled motor behavior, neurological status, and cognitive function. The task involves two oscillatory movements connected by a string. The snout oscillates to track the pendulum movement of the string produced by hand-over-hand oscillations of pulling, and so the snout guides the hands to grasp the string. The present study examines the allocation of time required to pull strings of varying diameter. Movement is also described with end-point measures, string-pulling topography with 2D markerless pose estimates based on transfer learning with deep neural networks, and Mat-lab image-segmentation and heuristic algorithms for object tracking. With reduced string diameter, mice took longer to pull 60 cm long strings. They also made more pulling cycles, misses, and mouth engagements, and displayed changes in the amplitude and frequency of pull cycles. The time measures agree with Fitts\u27s law in showing that increased task difficulty slows behavior and engages multiple compensatory sensorimotor modalities. The analysis reveals that time is a valuable resource in skilled motor behavior and information-theory can serve as a measure of its effective use

Correction: Data-driven analyses of motor impairments in animal models of neurological disorders.

[This corrects the article DOI: 10.1371/journal.pbio.3000516.]