A mild impairment in reversal learning in a bowl-digging substrate deterministic task but not other cognitive tests in the Dlg2+/- rat model of genetic risk for psychiatric disorder

Griesius, Simonas, Waldron, Sophie, Kamenish, Katie A., Cherbanich, Nick, Wilkinson, Lawrence S. ORCID: https://orcid.org/0000-0002-9337-6124, Thomas, Kerrie L. ORCID: https://orcid.org/0000-0003-3355-9583, Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009, Mellor, Jack R., Dwyer, Dominic M. ORCID: https://orcid.org/0000-0001-8069-5508 and Robinson, Emma S. J. 2023. A mild impairment in reversal learning in a bowl-digging substrate deterministic task but not other cognitive tests in the Dlg2+/- rat model of genetic risk for psychiatric disorder. Genes, Brain and Behavior 22 (6) , e12865. 10.1111/gbb.12865

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Abstract

Variations in the Dlg2 gene have been linked to increased risk for psychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability, bipolar disorder, attention deficit hyperactivity disorder, and pubertal disorders. Recent studies have reported disrupted brain circuit function and behaviour in models of Dlg2 knockout and haploinsufficiency. Specifically, deficits in hippocampal synaptic plasticity were found in heterozygous Dlg2+/- rats suggesting impacts on hippocampal dependent learning and cognitive flexibility. Here, we tested these predicted effects with a behavioural characterisation of the heterozygous Dlg2+/- rat model. Dlg2+/- rats exhibited a specific, mild impairment in reversal learning in a substrate deterministic bowl-digging reversal learning task. The performance of Dlg2+/- rats in other bowl digging task, visual discrimination and reversal, novel object preference, novel location preference, spontaneous alternation, modified progressive ratio, and novelty-suppressed feeding test were not impaired. These findings suggest that despite altered brain circuit function, behaviour across different domains is relatively intact in Dlg2+/- rats, with the deficits being specific to only one test of cognitive flexibility. The specific behavioural phenotype seen in this Dlg2+/- model may capture features of the clinical presentation associated with variation in the Dlg2 gene.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI) Psychology
Publisher:	Wiley Open Access
ISSN:	1601-1848
Date of First Compliant Deposit:	30 August 2023
Date of Acceptance:	25 August 2023
Last Modified:	27 Feb 2024 12:40
URI:	https://orca.cardiff.ac.uk/id/eprint/162109

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