{"title":"I型肌强直性营养不良(DM1) DMSXL小鼠模型逆转和消退学习改变:一项探索性研究","authors":"Sylvia Nieuwenhuis, Denys Kozakov, Kasia Kapusta, Geneviève Gourdon, Jeffrey C Glennon","doi":"10.1177/22143602251339350","DOIUrl":null,"url":null,"abstract":"<p><p>BackgroundCognitive changes in type 1 myotonic dystrophy (DM1) have a pronounced negative effect on quality of life measures. Despite this, the neural basis of these changes is poorly understood. DM1 patients demonstrate deficits in motivation and cognitive flexibility, reflective of apathy and obsessive-compulsive / autistic-like traits.ObjectiveThese traits can be readily assessed using reversal learning and appetitive extinction tasks. Reversal learning assesses the ability to learn following a change in a rule and can evaluate cognitive flexibility and habitual responding, while appetitive extinction assesses the ability to suppress a stimulus-action response following the change in the stimulus-reward relationship from rewarded to non-rewarded.MethodsIn this study we evaluated the performance of a mouse model of DM1, the DMSXL mouse in reversal learning and appetitive extinction tasks.ResultsSimilar to C57/BL6 wild type (WT) mice, DMSXL mice were able to learn stimulus reward relationships, however, in the late phase of reversal learning experiment DMSXL mice demonstrated increased habit-like behavior (increased number of correct responses). Following rule switching, DMSXL mice produced an increased number of errors compared to WT and showed increased latency to deliver correct responses. In the extinction task, DMSXL mice showed the ability to more rapidly extinguish a previously rewarded response than WT mice.ConclusionsThese findings constitute differences in cognitive flexibility, rule learning and motivation between DMSXL and WT mice which may inform our understanding of cognitive changes in DM1.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251339350"},"PeriodicalIF":3.2000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Altered reversal and extinction learning in the DMSXL mouse model of type I myotonic dystrophy (DM1): An exploratory study.\",\"authors\":\"Sylvia Nieuwenhuis, Denys Kozakov, Kasia Kapusta, Geneviève Gourdon, Jeffrey C Glennon\",\"doi\":\"10.1177/22143602251339350\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>BackgroundCognitive changes in type 1 myotonic dystrophy (DM1) have a pronounced negative effect on quality of life measures. Despite this, the neural basis of these changes is poorly understood. DM1 patients demonstrate deficits in motivation and cognitive flexibility, reflective of apathy and obsessive-compulsive / autistic-like traits.ObjectiveThese traits can be readily assessed using reversal learning and appetitive extinction tasks. Reversal learning assesses the ability to learn following a change in a rule and can evaluate cognitive flexibility and habitual responding, while appetitive extinction assesses the ability to suppress a stimulus-action response following the change in the stimulus-reward relationship from rewarded to non-rewarded.MethodsIn this study we evaluated the performance of a mouse model of DM1, the DMSXL mouse in reversal learning and appetitive extinction tasks.ResultsSimilar to C57/BL6 wild type (WT) mice, DMSXL mice were able to learn stimulus reward relationships, however, in the late phase of reversal learning experiment DMSXL mice demonstrated increased habit-like behavior (increased number of correct responses). Following rule switching, DMSXL mice produced an increased number of errors compared to WT and showed increased latency to deliver correct responses. In the extinction task, DMSXL mice showed the ability to more rapidly extinguish a previously rewarded response than WT mice.ConclusionsThese findings constitute differences in cognitive flexibility, rule learning and motivation between DMSXL and WT mice which may inform our understanding of cognitive changes in DM1.</p>\",\"PeriodicalId\":16536,\"journal\":{\"name\":\"Journal of neuromuscular diseases\",\"volume\":\" \",\"pages\":\"22143602251339350\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-05-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of neuromuscular diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/22143602251339350\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuromuscular diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/22143602251339350","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Altered reversal and extinction learning in the DMSXL mouse model of type I myotonic dystrophy (DM1): An exploratory study.
BackgroundCognitive changes in type 1 myotonic dystrophy (DM1) have a pronounced negative effect on quality of life measures. Despite this, the neural basis of these changes is poorly understood. DM1 patients demonstrate deficits in motivation and cognitive flexibility, reflective of apathy and obsessive-compulsive / autistic-like traits.ObjectiveThese traits can be readily assessed using reversal learning and appetitive extinction tasks. Reversal learning assesses the ability to learn following a change in a rule and can evaluate cognitive flexibility and habitual responding, while appetitive extinction assesses the ability to suppress a stimulus-action response following the change in the stimulus-reward relationship from rewarded to non-rewarded.MethodsIn this study we evaluated the performance of a mouse model of DM1, the DMSXL mouse in reversal learning and appetitive extinction tasks.ResultsSimilar to C57/BL6 wild type (WT) mice, DMSXL mice were able to learn stimulus reward relationships, however, in the late phase of reversal learning experiment DMSXL mice demonstrated increased habit-like behavior (increased number of correct responses). Following rule switching, DMSXL mice produced an increased number of errors compared to WT and showed increased latency to deliver correct responses. In the extinction task, DMSXL mice showed the ability to more rapidly extinguish a previously rewarded response than WT mice.ConclusionsThese findings constitute differences in cognitive flexibility, rule learning and motivation between DMSXL and WT mice which may inform our understanding of cognitive changes in DM1.
期刊介绍:
The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.