ChAT-ChR2-EYFP Mice Have Enhanced Motor Endurance But Show Deficits in Attention and Several Additional Cognitive Domains
Name
Kolisnyk-2013-mice have enhanced motor.pdf
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Author(s)
Kolisnyk, Benjamin
Guzman, Monica S.
Raulic, Sanda
Fan, Jue
Magalhaes, Ana C.
Feng, Guoping
Gros, Robert
Prado, Vania F.
Prado, Marco A. M.
Date Issued
June 2013
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Kolisnyk, B., M. S. Guzman, S. Raulic, J. Fan, A. C. Magalhaes, G. Feng, R. Gros, V. F. Prado, and M. A. M. Prado. “ChAT-ChR2-EYFP Mice Have Enhanced Motor Endurance But Show Deficits in Attention and Several Additional Cognitive Domains.” Journal of Neuroscience 33, no. 25 (June 19, 2013): 10427–10438.
Version
Final published version
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 (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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
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DOI of Published Version
https://doi.org/10.1523/JNEUROSCI.0395-13.2013
