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海马体中的多巴胺D1-D2信号传导介导趋近与回避行为。

Dopamine D1-D2 signalling in hippocampus arbitrates approach and avoidance.

作者信息

Godino Arthur, Salery Marine, Minier-Toribio Angelica M, Patel Vishwendra, Fullard John F, Kondev Veronika, Parise Eric M, Martinez-Rivera Freddyson J, Morel Carole, Roussos Panos, Blitzer Robert D, Nestler Eric J

机构信息

Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Aix-Marseille Université, INSERM, INMED, Marseille, France.

出版信息

Nature. 2025 May 7. doi: 10.1038/s41586-025-08957-5.

Abstract

The hippocampus, as well as dopamine circuits, coordinates decision-making in anxiety-eliciting situations. Yet, little is known about how dopamine modulates hippocampal representations of emotionally salient stimuli to inform appropriate resolution of approach versus avoidance conflicts. Here we studied dopaminoceptive neurons in the male mouse ventral hippocampus (vHipp), molecularly distinguished by their expression of dopamine D1 or D2 receptors. We show that these neurons are transcriptionally distinct and topographically organized across vHipp subfields and cell types. In the ventral subiculum where they are enriched, both D1 and D2 neurons are recruited during anxiogenic exploration, yet with distinct profiles related to investigation and behavioural selection. In turn, they mediate opposite approach-avoidance responses, and are differentially modulated by dopaminergic transmission in that region. Together, these results suggest that vHipp dopamine dynamics gate exploratory behaviours under contextual uncertainty, implicating dopaminoception in the complex computation engaged in the vHipp to govern emotional states.

摘要

海马体以及多巴胺回路在引发焦虑的情境中协调决策。然而,关于多巴胺如何调节情绪显著刺激的海马体表征以指导适当解决趋近与回避冲突,我们所知甚少。在这里,我们研究了雄性小鼠腹侧海马体(vHipp)中的多巴胺感受神经元,它们通过表达多巴胺D1或D2受体在分子水平上得以区分。我们发现,这些神经元在转录上是不同的,并且在vHipp亚区和细胞类型中呈拓扑组织分布。在它们富集的腹侧下托,D1和D2神经元在致焦虑探索过程中均被招募,但与探究和行为选择相关的表现不同。反过来,它们介导相反的趋近-回避反应,并在该区域受到多巴胺能传递的不同调节。总之,这些结果表明,vHipp多巴胺动态在情境不确定性下控制探索行为,这意味着多巴胺感受参与了vHipp中用于调节情绪状态的复杂计算。

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