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。

IF 2.7 4区 医学 Q3 NEUROSCIENCES European Journal of Neuroscience Pub Date : 2024-10-31 DOI:10.1111/ejn.16584
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
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引用次数: 0

摘要

认知灵活性是一种使行为适应环境变化的能力,在包括精神分裂症和帕金森病在内的一系列脑部疾病中都会受到损害。认知灵活性的推测神经基底包括通往腹侧纹状体(VS)和背内侧纹状体(DMS)的间脑通路。然而,目前还不清楚通向腹侧纹状体和背侧纹状体的间脑投射对灵活的奖赏相关学习的贡献是否不同。在这里,大鼠获得了一个双选空间概率逆转学习(PRL)任务,在80%|20%的基础上强化(正确|不正确的反应),以评估行为对反应-结果或然性重复逆转的灵活性。我们报告说,当光刺激与负反馈(即奖赏遗漏)在时间上一致时,从腹侧被盖区(VTA)到VS中的伏隔核(NAcS)投射的光遗传刺激会显著损害逆转学习。在行为任务的其他阶段刺激 VTA → NAcS 没有明显效果。从黑质(SN)到DMS的投射神经元的光遗传刺激,无论是与奖励接收或遗漏相一致,还是在做出选择之前,对逆转学习都没有显著影响。这些发现与以下观点一致:VTA → NAcS通路的活动增加会损害负强化学习,从而破坏行为的灵活性。
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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.

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来源期刊
European Journal of Neuroscience
European Journal of Neuroscience 医学-神经科学
CiteScore
7.10
自引率
5.90%
发文量
305
审稿时长
3.5 months
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.
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