Simonas Griesius, Sophie Waldron, Katie A. Kamenish, Nick Cherbanich, Lawrence S. Wilkinson, Kerrie L. Thomas, Jeremy Hall, Jack R. Mellor, Dominic M. Dwyer, Emma S. J. Robinson
{"title":"Dlg2+/- 精神疾病遗传风险模型大鼠在掘碗底物确定性任务中的逆向学习能力受到轻微损伤,但其他认知测试能力并未受到损伤","authors":"Simonas Griesius, Sophie Waldron, Katie A. Kamenish, Nick Cherbanich, Lawrence S. Wilkinson, Kerrie L. Thomas, Jeremy Hall, Jack R. Mellor, Dominic M. Dwyer, Emma S. J. Robinson","doi":"10.1111/gbb.12865","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12865","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"Simonas Griesius, Sophie Waldron, Katie A. Kamenish, Nick Cherbanich, Lawrence S. Wilkinson, Kerrie L. Thomas, Jeremy Hall, Jack R. Mellor, Dominic M. Dwyer, Emma S. J. Robinson\",\"doi\":\"10.1111/gbb.12865\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":50426,\"journal\":{\"name\":\"Genes Brain and Behavior\",\"volume\":\"22 6\",\"pages\":\"\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2023-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12865\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genes Brain and Behavior\",\"FirstCategoryId\":\"102\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/gbb.12865\",\"RegionNum\":4,\"RegionCategory\":\"心理学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes Brain and Behavior","FirstCategoryId":"102","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/gbb.12865","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
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
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.
期刊介绍:
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