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Deletion of the vesicular acetylcholine transporter from pedunculopontine/laterodorsal tegmental neurons modifies gait
Author(s) -
Janickova Helena,
Rosborough Kaie,
AlOnaizi Mohammed,
Kljakic Ornela,
Guzman Monica S.,
Gros Robert,
Prado Marco A. M.,
Prado Vania F.
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13910
Subject(s) - vesicular acetylcholine transporter , cholinergic , neuroscience , cholinergic neuron , pedunculopontine tegmental nucleus , pedunculopontine nucleus , psychology , biology , medicine , parkinson's disease , choline acetyltransferase , deep brain stimulation , disease
Postural instability and gait disturbances, common disabilities in the elderly and frequently present in Parkinson's disease ( PD ), have been suggested to be related to dysfunctional cholinergic signaling in the brainstem. We investigated how long‐term loss of cholinergic signaling from mesopontine nuclei influence motor behaviors. We selectively eliminated the vesicular acetylcholine transporter ( VAC hT) in pedunculopontine and laterodorsal tegmental nuclei cholinergic neurons to generate mice with selective mesopontine cholinergic deficiency ( VAC h T E n1‐Cre‐flox/flox ). VAC h T E n1‐Cre‐flox/flox mice did not show any gross health or neuromuscular abnormality on metabolic cages, wire‐hang and grip‐force tests. Young VAC h T E n1‐Cre‐flox/flox mice (2–5 months‐old) presented motor learning/coordination deficits on the rotarod; moved slower, and had smaller steps on the catwalk, but showed no difference in locomotor activity on the open field. Old VAC h T E n1‐Creflox/flox mice (13–16 months‐old) showed more pronounced motor learning/balance deficits on the rotarod, and more pronounced balance deficits on the catwalk. Furthermore, old mutants moved faster than controls, but with similar step length. Additionally, old VAC hT‐deficient mice were hyperactive. These results suggest that dysfunction of cholinergic neurons from mesopontine nuclei, which is commonly seen in PD , has causal roles in motor functions. Prevention of mesopontine cholinergic failure may help to prevent/improve postural instability and falls in PD patients.Read the Editorial Highlight for this article on page 688.