Reviewer #1 (Public Review): Restoration of locomotor function following stimulation of the A13 region in Parkinson’s mouse models
Year: 2023
Type: peer-review
Abstract: Parkinson’s disease (PD) is characterized by extensive motor and non-motor dysfunction, including gait disturbance, which is difficult to treat effectively. This study explores the therapeutic potential of targeting the A13 region, a dopamine-containing area of the medial zona incerta (mZI) that has shown relative preservation in PD models. The A13 is identified to project to the mesencephalic locomotor region (MLR), with a subpopulation of cells displaying activity correlating to movement speed, suggesting its potential involvement in locomotor function. We show that photoactivation of this region can alleviate bradykinesia and akinetic symptoms in a mouse model of PD, revealing the presence of preserved parallel motor pathways for movement. We identified areas of preservation and plasticity within the mZI connectome using whole-brain imaging. Our findings suggest a global remodeling of afferent and efferent projections of the A13 region, highlighting the zona incerta’s role as a crucial hub for the rapid selection of motor function. Despite endogenous compensatory mechanisms proving insufficient to overcome locomotor deficits in PD, our data demonstrate that photostimulation of the A13 region effectively restores locomotor activity. The study unveils the significant pro-locomotor effects of the A13 region and suggests its promising potential as a therapeutic target for PD-related gait dysfunction.This work examines the function of the A13 nucleus in locomotion, an area with direct connectivity to locomotor regions in the brainstem. Our work shows that A13 stimulation can restore locomotor function and improve bradykinesia symptoms in a PD mouse model.
Authors: Linda H Kim, Adam Lognon, Sandeep Sharma, Michelle A. Tran, Taylor Chomiak, Stephanie Tam, Claire McPherson, Shane E. A. Eaton, Zelma H. T. Kiss, Patrick J. Whelan
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4388233644