Katharina Zühlsdorff, Júlia Sala-Bayo, Sammy Piller, Peter Zhukovsky, Thorsten Lamla, Wiebke Nissen, Moritz von Heimendahl, Serena Deiana, Janet R Nicholson, Trevor W Robbins, Johan Alsiö, Jeffrey W Dalley
{"title":"通过光遗传激活间脑投射到伏隔核外壳,破坏负强化学习,从而损害概率性逆转学习。","authors":"Katharina Zühlsdorff, Júlia Sala-Bayo, Sammy Piller, Peter Zhukovsky, Thorsten Lamla, Wiebke Nissen, Moritz von Heimendahl, Serena Deiana, Janet R Nicholson, Trevor W Robbins, Johan Alsiö, Jeffrey W Dalley","doi":"10.1111/ejn.16584","DOIUrl":null,"url":null,"abstract":"<p><p>Cognitive flexibility, the capacity to adapt behaviour to changes in the environment, is impaired in a range of brain disorders, including schizophrenia and Parkinson's disease. Putative neural substrates of cognitive flexibility include mesencephalic pathways to the ventral striatum (VS) and dorsomedial striatum (DMS), hypothesized to encode learning signals needed to maximize rewarded outcomes during decision-making. However, it is unclear whether mesencephalic projections to the ventral and dorsal striatum are distinct in their contribution to flexible reward-related learning. Here, rats acquired a two-choice spatial probabilistic reversal learning (PRL) task, reinforced on an 80%|20% basis (correct|incorrect responses) that assessed the flexibility of behaviour to repeated reversals of response-outcome contingencies. We report that optogenetic stimulation of projections from the ventral tegmental area (VTA) to the nucleus accumbens shell (NAcS) in the VS significantly impaired reversal learning when optical stimulation was temporally aligned with negative feedback (i.e., reward omission). VTA → NAcS stimulation during other phases of the behavioural task was without significant effect. Optogenetic stimulation of projection neurons from the substantia nigra (SN) to the DMS, aligned either with reward receipt or omission or prior to making a choice, had no significant effect on reversal learning. These findings are consistent with the notion that increased activity in the VTA → NAcS pathway disrupts behavioural flexibility by impairing learning from negative reinforcement.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Optogenetic activation of mesencephalic projections to the nucleus accumbens shell impairs probabilistic reversal learning by disrupting learning from negative reinforcement.\",\"authors\":\"Katharina Zühlsdorff, Júlia Sala-Bayo, Sammy Piller, Peter Zhukovsky, Thorsten Lamla, Wiebke Nissen, Moritz von Heimendahl, Serena Deiana, Janet R Nicholson, Trevor W Robbins, Johan Alsiö, Jeffrey W Dalley\",\"doi\":\"10.1111/ejn.16584\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cognitive flexibility, the capacity to adapt behaviour to changes in the environment, is impaired in a range of brain disorders, including schizophrenia and Parkinson's disease. Putative neural substrates of cognitive flexibility include mesencephalic pathways to the ventral striatum (VS) and dorsomedial striatum (DMS), hypothesized to encode learning signals needed to maximize rewarded outcomes during decision-making. However, it is unclear whether mesencephalic projections to the ventral and dorsal striatum are distinct in their contribution to flexible reward-related learning. Here, rats acquired a two-choice spatial probabilistic reversal learning (PRL) task, reinforced on an 80%|20% basis (correct|incorrect responses) that assessed the flexibility of behaviour to repeated reversals of response-outcome contingencies. We report that optogenetic stimulation of projections from the ventral tegmental area (VTA) to the nucleus accumbens shell (NAcS) in the VS significantly impaired reversal learning when optical stimulation was temporally aligned with negative feedback (i.e., reward omission). VTA → NAcS stimulation during other phases of the behavioural task was without significant effect. Optogenetic stimulation of projection neurons from the substantia nigra (SN) to the DMS, aligned either with reward receipt or omission or prior to making a choice, had no significant effect on reversal learning. These findings are consistent with the notion that increased activity in the VTA → NAcS pathway disrupts behavioural flexibility by impairing learning from negative reinforcement.</p>\",\"PeriodicalId\":11993,\"journal\":{\"name\":\"European Journal of Neuroscience\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-10-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/ejn.16584\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ejn.16584","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Optogenetic activation of mesencephalic projections to the nucleus accumbens shell impairs probabilistic reversal learning by disrupting learning from negative reinforcement.
Cognitive flexibility, the capacity to adapt behaviour to changes in the environment, is impaired in a range of brain disorders, including schizophrenia and Parkinson's disease. Putative neural substrates of cognitive flexibility include mesencephalic pathways to the ventral striatum (VS) and dorsomedial striatum (DMS), hypothesized to encode learning signals needed to maximize rewarded outcomes during decision-making. However, it is unclear whether mesencephalic projections to the ventral and dorsal striatum are distinct in their contribution to flexible reward-related learning. Here, rats acquired a two-choice spatial probabilistic reversal learning (PRL) task, reinforced on an 80%|20% basis (correct|incorrect responses) that assessed the flexibility of behaviour to repeated reversals of response-outcome contingencies. We report that optogenetic stimulation of projections from the ventral tegmental area (VTA) to the nucleus accumbens shell (NAcS) in the VS significantly impaired reversal learning when optical stimulation was temporally aligned with negative feedback (i.e., reward omission). VTA → NAcS stimulation during other phases of the behavioural task was without significant effect. Optogenetic stimulation of projection neurons from the substantia nigra (SN) to the DMS, aligned either with reward receipt or omission or prior to making a choice, had no significant effect on reversal learning. These findings are consistent with the notion that increased activity in the VTA → NAcS pathway disrupts behavioural flexibility by impairing learning from negative reinforcement.
期刊介绍:
EJN is the journal of FENS and supports the international neuroscientific community by publishing original high quality research articles and reviews in all fields of neuroscience. In addition, to engage with issues that are of interest to the science community, we also publish Editorials, Meetings Reports and Neuro-Opinions on topics that are of current interest in the fields of neuroscience research and training in science. We have recently established a series of ‘Profiles of Women in Neuroscience’. Our goal is to provide a vehicle for publications that further the understanding of the structure and function of the nervous system in both health and disease and to provide a vehicle to engage the neuroscience community. As the official journal of FENS, profits from the journal are re-invested in the neuroscientific community through the activities of FENS.