期刊
JOURNAL OF NEUROSCIENCE
卷 33, 期 25, 页码 10427-10438出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0395-13.2013
关键词
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资金
- Canadian Institutes of Health Research [MOP89919, 126000]
- Natural Sciences and Engineering Research Council of Canada
- Heart and Stroke Foundation of Ontario [NA 6656]
- Canada Foundation for Innovation
- Ontario Research Fund
- Heart and Stroke Foundation of Canada
Acetylcholine (ACh) is an important neuromodulator in the nervous system implicated inmanyforms 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.
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