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Altered motor, anxiety-related and attentional task performance at baseline associate with multiple gene copies of the vesicular acetylcholine transporter and related protein overexpression in ChAT::Cre+ rats

Lookup NU author(s): Dr Joanna Elson



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019, The Author(s).Transgenic rodents expressing Cre recombinase cell specifically are used for exploring mechanisms regulating behavior, including those mediated by cholinergic signaling. However, it was recently reported that transgenic mice overexpressing a bacterial artificial chromosome containing choline acetyltransferase (ChAT) gene, for synthesizing the neurotransmitter acetylcholine, present with multiple vesicular acetylcholine transporter (VAChT) gene copies, resulting in altered cholinergic tone and accompanying behavioral abnormalities. Since ChAT::Cre+ rats, used increasingly for understanding the biological basis of CNS disorders, utilize the mouse ChAT promotor to control Cre recombinase expression, we assessed for similar genotypical and phenotypical differences in such rats compared to wild-type siblings. The rats were assessed for mouse VAChT copy number, VAChT protein expression levels and for sustained attention, response control and anxiety. Rats were also subjected to a contextual fear conditioning paradigm using an unconditional fear-inducing stimulus (electrical foot shocks), with blood samples taken at baseline, the fear acquisition phase and retention testing, for measuring blood plasma markers of hypothalamic–pituitary–adrenal gland (HPA)-axis activity. ChAT::Cre+ rats expressed multiple mouse VAChT gene copies, resulting in significantly higher VAChT protein expression, revealed anxiolytic behavior, hyperlocomotion and deficits in tasks requiring sustained attention. The HPA-axis was intact, with unaltered circulatory levels of acute stress-induced corticosterone, leptin and glucose. Our findings, therefore, reveal that in ChAT::Cre+ rats, VAChT overexpression associates with significant alterations of certain cognitive, motor and affective functions. Although highly useful as an experimental tool, it is essential to consider the potential effects of altered cholinergic transmission on baseline behavior in ChAT::Cre rats.

Publication metadata

Author(s): Mantanona CP, Alsio J, Elson JL, Fisher BM, Dalley JW, Bussey T, Pienaar IS

Publication type: Article

Publication status: Published

Journal: Brain Structure and Function

Year: 2019

Volume: 224

Issue: 9

Pages: 3095–3116

Print publication date: 01/12/2019

Online publication date: 10/09/2019

Acceptance date: 03/09/2019

Date deposited: 21/01/2020

ISSN (print): 1863-2653

ISSN (electronic): 1863-2661

Publisher: Springer Verlag


DOI: 10.1007/s00429-019-01957-y

PubMed id: 31506825


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