Anatomy and Cell Biology Publications

Title

ChAT-ChR2-EYFP Mice Have Enhanced Motor Endurance But Show Deficits in Attention and Several Additional Cognitive Domains

Document Type

Article

Publication Date

6-19-2013

Journal

JOURNAL OF NEUROSCIENCE

Volume

33

Issue

25

First Page

10427

Last Page

10438

URL with Digital Object Identifier

10.1523/JNEUROSCI.0395-13.2013

Abstract

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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