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- Title
ChA T-ChR2-EYFP Mice Have Enhanced Motor Endurance But Show Deficits in Attention and Several Additional Cognitive Domains.
- Authors
Kolisnyk, Benjamin; Guzman, Monica S.; Raulic, Sanda; Fan, Jue; Magalhaes, Ana C.; Feng, Guoping; Gros, Robert; Prado, Vania F.; Prado, Marco A. M.
- Abstract
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 (Ch AT) promoter (ChA T-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 dem-onstrate 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 ChA T-ChR2-EYFP mice show altered cholinergic tone that fundamentally differentiates them from wild-type mice.
- Subjects
ACETYLCHOLINE; GROWTH associated protein-43; LABORATORY mice; COGNITIVE neuroscience; GENE expression; RHODOPSIN; ATTENTION-deficit hyperactivity disorder
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 25, p10427
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0395-13.2013