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J Neurosci DOI:10.1523/JNEUROSCI.0395-13.2013

ChAT-ChR2-EYFP mice have enhanced motor endurance but show deficits in attention and several additional cognitive domains.

Publication TypeJournal Article
Year of Publication2013
AuthorsKolisnyk, B, Guzman, MS, Raulic, S, Fan, J, Magalhães, AC, Feng, G, Gros, R, Prado, VF, Prado, MAM
JournalJ Neurosci
Date Published2013 Jun 19
KeywordsAnimals, Anxiety, Attention, Blotting, Western, Choline O-Acetyltransferase, Cognition, Fluorescent Antibody Technique, Glucose Tolerance Test, Hand Strength, Hindlimb Suspension, Maze Learning, Metabolism, Mice, Mice, Transgenic, Parasympathetic Nervous System, Physical Endurance, Polymerase Chain Reaction, Postural Balance, Psychomotor Performance, Reaction Time, Rhodopsin, Swimming, Vesicular Acetylcholine Transport Proteins

Acetylcholine (ACh) is an important neuromodulator in the nervous system implicated in many forms of cognitive and motor processing. Recent studies have used bacterial artificial chromosome (BAC) transgenic mice expressing channelrhodopsin-2 (ChR2) protein under the control of the choline acetyltransferase (ChAT) promoter (ChAT-ChR2-EYFP) to dissect cholinergic circuit connectivity and function using optogenetic approaches. We report that a mouse line used for this purpose also carries several copies of the vesicular acetylcholine transporter gene (VAChT), which leads to overexpression of functional VAChT and consequently increased cholinergic tone. We demonstrate that these mice have marked improvement in motor endurance. However, they also present severe cognitive deficits, including attention deficits and dysfunction in working memory and spatial memory. These results suggest that increased VAChT expression may disrupt critical steps in information processing. Our studies demonstrate that ChAT-ChR2-EYFP mice show altered cholinergic tone that fundamentally differentiates them from wild-type mice.


Alternate JournalJ. Neurosci.
PubMed ID23785154
Grant ListMOP 126000 / / Canadian Institutes of Health Research / Canada
MOP 89919 / / Canadian Institutes of Health Research / Canada