title: B6eGFPChAT mice overexpressing the vesicular acetylcholine transporter exhibit spontaneous hypoactivity and enhanced exploration in novel environments.
abstract: Cholinergic innervation is extensive throughout the central and peripheral nervous systems. Among its many roles, the neurotransmitter acetylcholine (ACh) contributes to the regulation of motor function, locomotion, and exploration. Cholinergic deficits and replacement strategies have been investigated in neurodegenerative disorders, particularly in cases of Alzheimer's disease (AD). Focus has been on blocking acetylcholinesterase (AChE) and enhancing ACh synthesis to improve cholinergic neurotransmission. As a first step in evaluating the physiological effects of enhanced cholinergic function through the upregulation of the vesicular acetylcholine transporter (VAChT), we used the hypercholinergic B6eGFPChAT congenic mouse model that has been shown to contain multiple VAChT gene copies. Analysis of biochemical and behavioral paradigms suggest that modest increases in VAChT expression can have a significant effect on spontaneous locomotion, reaction to novel stimuli, and the adaptation to novel environments. These observations support the potential of VAChT as a therapeutic target to enhance cholinergic tone, thereby decreasing spontaneous hyperactivity and increasing exploration in novel environments.
authors.affiliation: Brain Sciences, Biological Sciences, Sunnybrook Research Institute 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Nagy
authors.affiliation: Brain Sciences, Biological Sciences, Sunnybrook Research Institute 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aubert
keywords: Choline acetyltransferase; VAChT; cholinergic; eGFP-ChAT; exploration; locomotion