Affiliation:
1. Département de Pharmacologie-Physiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Canada
2. Centre de recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada
3. Neurosciences Sherbrooke, Sherbrooke, Canada
4. Institut de Pharmacologie de Sherbrooke, Sherbrooke, Canada
Abstract
The mesencephalic locomotor region (MLR) controls locomotion in vertebrates. In humans with Parkinson disease, locomotor deficits are increasingly associated with decreased activity in the MLR. This brainstem region, commonly considered to include the cuneiform and pedunculopontine nuclei, has been explored as a target for deep brain stimulation to improve locomotor function, but the results are variable, from modest to promising. However, the MLR is a heterogeneous structure, and identification of the best cell type to target is only beginning. Here, I review the studies that uncovered the role of genetically defined MLR cell types, and I highlight the cells whose activation improves locomotor function in animal models of Parkinson disease. The promising cell types to activate comprise some glutamatergic neurons in the cuneiform and caudal pedunculopontine nuclei, as well as some cholinergic neurons of the pedunculopontine nucleus. Activation of MLR GABAergic neurons should be avoided, since they stop locomotion or evoke bouts flanked with numerous stops. The MLR is also considered a potential target in spinal cord injury, supranuclear palsy, primary progressive freezing of gait, or stroke. Better targeting of the MLR cell types should be achieved through optimized deep brain stimulation protocols, pharmacotherapy, or the development of optogenetics for human use.
Funder
Faculté de médecine et des sciences de la santé
Fonds Jean-Luc Mongrain de la fondation du CHUS
H2020 European Research Council
Canada Foundation for Innovation
Natural Sciences and Engineering Research Council of Canada
Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke
Canadian Institutes of Health Research
Centre d’excellence en Neurosciences de l’Université de Sherbrooke
Fonds de la Recherche du Québec - Santé
Subject
Neurology (clinical),General Neuroscience
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献