Cholinergic upregulation by optogenetic stimulation of nucleus basalis after photothrombotic stroke in forelimb somatosensory cortex improves endpoint and motor but not sensory control of skilled reaching in mice

Abstract

A network of cholinergic neurons in the basal forebrain innerve the forebrain and are proposed to contribute to a variety of functions including attention, and cortical plasticity. This study examined the contribution of the nucleus basalis cholinergic projection to the sensorimotor cortex on recovery on a skilled reach-to-eat task following photothrombotic stroke in the forelimb region of the somatosensory cortex. Mice were trained to perform a single-pellet skilled reaching task and their pre and poststroke performance, from Day 4 to Day 28 poststroke, was assessed frame-by-frame by video analysis with end point, movement and sensorimotor integration measures. Somatosensory forelimb lesions produced impairments in endpoint and movement component measures of reaching and increased the incidence of fictive eating, a sensory impairment in mistaking a missed reach for a successful reach. Upregulated acetylcholine (ACh) release, as measured by local field potential recording, elicited via optogenetic stimulation of the nucleus basalis improved recovery of reaching and improved movement scores but did not affect a sensorimotor integration impairment poststroke. The resultsshow that the mouse cortical forelimb somatosensory region contributes to forelimb motor behavior and suggest that ACh upregulation could serve as an adjunct to behavioral therapy for the acute treatment of stroke.Key Words: acetylcholine upregulation, optogenetic stimulation of the nucleus basalis cholinergic neurons, photothrombotic stroke, sensory neglect, skilled reaching task in mice

Closed-loop automated reaching apparatus (CLARA) for interrogating complex motor behaviors

“…Detailed 3D motion tracking Skilled reach behavior has been a widely characterized motor behavior paradigm for decades (Gonzalez et al 2004, Whishaw et al 2008, Becker and Person 2019, and is commonly used to model rehabilitation and recovery from neurologic injury (Ryait et al 2019). However, due to the unconstrained nature of the task (Jarratt and Hyland 1999, Buitrago et al 2004, Whishaw et al 2017, researchers are often limited to qualitative descriptions of the behavior (Whishaw et al 2008, Agha et al 2020. Markerless pose tracking from the CLARA system was used to accurately plot the outward (purple) and return (blue) trajectories of each reach from multiple cameras (figure 4(A)).…”