Experimental investigation into the role of the subthalamic nucleus (STN) in motor control using optogenetics in mice.
Brain Research. 2021-03-01; 1755: 147226
DOI: 10.1016/j.brainres.2020.147226
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1. Brain Res. 2021 Mar 15;1755:147226. doi: 10.1016/j.brainres.2020.147226. Epub
2020 Dec 23.
Experimental investigation into the role of the subthalamic nucleus (STN) in
motor control using optogenetics in mice.
Guillaumin A(1), Serra GP(1), Georges F(2), Wallén-Mackenzie Å(3).
Author information:
(1)Department of Organism Biology, Uppsala University, SE-752 36 Uppsala,
Sweden.
(2)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France.
(3)Department of Organism Biology, Uppsala University, SE-752 36 Uppsala,
Sweden. Electronic address: .
The subthalamic nucleus (STN) is critical for the execution of intended
movements. Loss of its normal function is strongly associated with several
movement disorders, including Parkinson’s disease for which the STN is an
important target area in deep brain stimulation (DBS) therapy. Classical basal
ganglia models postulate that two parallel pathways, the direct and indirect
pathways, exert opposing control over movement, with the STN acting within the
indirect pathway. The STN is regulated by both inhibitory and excitatory input,
and is itself excitatory. While most functional knowledge of this clinically
relevant brain structure has been gained from pathological conditions and
models, primarily parkinsonian, experimental evidence for its role in normal
motor control has remained more sparse. The objective here was to tease out the
selective impact of the STN on several motor parameters required to achieve
intended movement, including locomotion, balance and motor coordination.
Optogenetic excitation and inhibition using both bilateral and unilateral
stimulations of the STN were implemented in freely-moving mice. The results
demonstrate that selective optogenetic inhibition of the STN enhances locomotion
while its excitation reduces locomotion. These findings lend experimental
support to basal ganglia models of the STN in terms of locomotion. In addition,
optogenetic excitation in freely-exploring mice induced self-grooming, disturbed
gait and a jumping/escaping behavior, while causing reduced motor coordination
in advanced motor tasks, independent of grooming and jumping. This study
contributes experimentally validated evidence for a regulatory role of the STN
in several aspects of motor control.
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
DOI: 10.1016/j.brainres.2020.147226
PMID: 33358727 [Indexed for MEDLINE]