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.

Autor: Griesius S; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol, UK., Waldron S; Neuroscience and Mental Health Research Institute, Psychology, Cardiff, UK.; Department of Psychology, Cardiff, UK., Kamenish KA; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol, UK., Cherbanich N; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol, UK., Wilkinson LS; Neuroscience and Mental Health Research Institute, Psychology, Cardiff, UK.; Department of Psychology, Cardiff, UK.; MRC Centre for Neuropsychiatric Genetics and Genomics, Schools of Medicine and Genetics and Genomics, Schools of Medicine and Psychology, Cardiff, UK., Thomas KL; Neuroscience and Mental Health Research Institute, Psychology, Cardiff, UK.; Department of Medicine and Psychology, Cardiff, UK., Hall J; Neuroscience and Mental Health Research Institute, Psychology, Cardiff, UK.; MRC Centre for Neuropsychiatric Genetics and Genomics, Schools of Medicine and Genetics and Genomics, Schools of Medicine and Psychology, Cardiff, UK.; Department of Medicine and Psychology, Cardiff, UK., Mellor JR; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol, UK., Dwyer DM; Neuroscience and Mental Health Research Institute, Psychology, Cardiff, UK.; Department of Psychology, Cardiff, UK., Robinson ESJ; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol, UK.
Jazyk: angličtina
Zdroj: Genes, brain, and behavior [Genes Brain Behav] 2023 Dec; Vol. 22 (6), pp. e12865. Date of Electronic Publication: 2023 Sep 13.
DOI: 10.1111/gbb.12865
Abstrakt: 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.
(© 2023 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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