The schizophrenia risk gene Map2k7 regulates responding in a novel contingency-shifting rodent touchscreen gambling task

Openshaw, R. L. , Pratt, J. A. and Morris, B. J. (2022) The schizophrenia risk gene Map2k7 regulates responding in a novel contingency-shifting rodent touchscreen gambling task. Disease Models and Mechanisms, 15(3), dmm049310. (doi: 10.1242/dmm.049310) (PMID:35275161) (PMCID:PMC8922023)

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In schizophrenia, subjects show reduced ability to evaluate and update risk/reward contingencies, showing correspondingly suboptimal performance in the Iowa gambling task. JNK signalling gene variants are associated with schizophrenia risk, and JNK modulates aspects of cognition. We therefore studied the performance of mice hemizygous for genetic deletion of the JNK activator MKK7 (Map2k7+/− mice) in a touchscreen version of the Iowa gambling task, additionally incorporating a novel contingency-switching stage. Map2k7+/− mice performed slightly better than wild-type (WT) littermates in acquisition and performance of the task. Although Map2k7+/− mice adapted well to subtle changes in risk/reward contingencies, they were profoundly impaired when the positions of ‘best’ and ‘worst’ choice selections were switched, and still avoided the previous ‘worst’ choice location weeks after the switch. This demonstrates a precise role for MKK7–JNK signalling in flexibility of risk/reward assessment and suggests that genetic variants affecting this molecular pathway may underlie impairment in this cognitive domain in schizophrenia. Importantly, this new contingency shift adaptation of the rodent touchscreen gambling task has translational utility for characterising these cognitive subprocesses in models of neuropsychiatric disorders.

Item Type:Articles
Additional Information:This work was supported by the Medical Research Council (UK), award no. MR/ K501335/1.
Glasgow Author(s) Enlighten ID:Openshaw, Rebecca Louise and Pratt, Dr Judith and Morris, Professor Brian
Authors: Openshaw, R. L., Pratt, J. A., and Morris, B. J.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Disease Models and Mechanisms
Publisher:The Company of Biologists
ISSN (Online):1754-8411
Published Online:11 March 2022
Copyright Holders:Copyright © 2022 The Company of Biologists Ltd
First Published:First published in Disease Models and Mechanisms 15(3): dmm049310
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190660MRC Doctoral Training Grant 2013/14 and 2014/15George BaillieMedical Research Council (MRC)MR/K501335/1MVLS - Graduate School