纳什家族神经科学系和弗里德曼大脑研究所Nestler, Eric J.小组的一项最新研究揭示了海马多巴胺D1-D2信号决定了趋近和回避。该项研究成果发表在2025年5月7日出版的《自然》上。

本文研究了雄性母主题腹侧海马（vHipp）中的多巴胺感觉神经元，这些神经元通过表达多巴胺D1或D2受体进行分子区分。研究团队发现这些神经元在转录上是不同的，并且在vHipp子场和细胞类型上有地形组织。在腹侧枕下，D1和D2神经元都在焦虑性探索过程中被招募，但在调查和行为选择方面具有不同的特征。反过来，它们介导相反的接近-回避反应，并由该区域的多巴胺能传递差异调节。综上所述，这些结果表明，vHipp多巴胺动力学控制了情境不确定性下的探索性行为，暗示了在vHipp参与的复杂计算中，多巴胺感觉控制着情绪状态。

据悉，海马体，以及多巴胺回路，在引发焦虑的情况下协调决策。然而，关于多巴胺如何调节海马对情绪显著刺激的表征，以告知适当的解决方法与避免冲突，课题组知之甚少。

附：英文原文

Title: Dopamine D1–D2 signalling in hippocampus arbitrates approach and avoidance

Author: 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.

Issue&Volume: 2025-05-07

Abstract: The hippocampus1,2,3,4,5,6, as well as dopamine circuits7,8,9, 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.

DOI: 10.1038/s41586-025-08957-5

Source: https://www.nature.com/articles/s41586-025-08957-5