title: ChAT-ChR2-EYFP mice have enhanced motor endurance but show deficits in attention and several additional cognitive domains.
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.
authors.affiliation: Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5K8.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kolisnyk
authors.forename: Monica S
authors.initials: MS
authors.lastname: Guzman
authors.forename: Sanda
authors.initials: S
authors.lastname: Raulic
authors.forename: Jue
authors.initials: J
authors.lastname: Fan
authors.forename: Ana C
authors.initials: AC
authors.lastname: Magalhães
authors.forename: Guoping
authors.initials: G
authors.lastname: Feng
authors.forename: Robert
authors.initials: R
authors.lastname: Gros
authors.forename: Vania F
authors.initials: VF
authors.lastname: Prado
authors.forename: Marco A M
authors.initials: MA
authors.lastname: Prado
mesh_terms: D000818:Animals; D001007:Anxiety / Q000523:psychology; D001288:Attention / Q000502:physiology*; D015153:Blotting, Western; D000075402:Channelrhodopsins; D002795:Choline O-Acetyltransferase / Q000235:genetics* / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005951:Glucose Tolerance Test; D018737:Hand Strength / Q000502:physiology; D019417:Hindlimb Suspension; D018782:Maze Learning / Q000502:physiology; D008660:Metabolism / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010275:Parasympathetic Nervous System / Q000502:physiology; D010807:Physical Endurance / Q000235:genetics* / Q000502:physiology*; D016133:Polymerase Chain Reaction; D004856:Postural Balance / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D013550:Swimming / Q000502:physiology; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D000075402:Channelrhodopsins; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D002795:Choline O-Acetyltransferase