美国加州大学Kheirbek, Mazen A.团队报道了控制快感缺乏的压力神经编码。这一研究成果发表在2024年12月4日出版的国际学术期刊《自然》上。

据介绍，快感缺乏，即寻求、重视和学习奖励的动力减弱，是重度抑郁症的一个核心特征。快感缺乏的神经基础以及这种情绪状态如何驱动行为尚不清楚。

该团队研究了快感缺乏症的神经编码，利用了这样一个事实，即当小鼠暴露于创伤性社会压力时，易受影响的动物变得社交退缩和快感缺乏症，而其他动物则保持弹性。通过高密度电生理记录基底外侧杏仁核（BLA）和腹侧CA1 （vCA1）的神经活动模式，该研究组确定了敏感性和弹性的神经特征。当小鼠积极寻求奖励时，弹性小鼠的BLA活动表现出对奖励选择的明显区别。

相比之下，敏感小鼠表现出类似反刍的特征，其中BLA神经元编码了切换或停留在先前选择的奖励上的意图。在易感小鼠中，vCA1输入到BLA的操作挽救了功能失调的神经动力学，放大了与弹性相关的动力学，并逆转了快感缺乏行为。最后，当动物休息时，易感小鼠的自发BLA活动显示出更多不同的神经种群状态。这种自发的活动使他们能够解码群体身份，并推断出一个主题是否有压力史，比单独的行为结果更好。

这项工作揭示了群体水平的神经动力学，解释了个体对创伤应激反应的差异，并表明调节vCA1-BLA输入可以通过调节这些动态来增强恢复力。

附：英文原文

Title: Understanding the neural code of stress to control anhedonia

Author: Xia, Frances, Fascianelli, Valeria, Vishwakarma, Nina, Ghinger, Frances Grace, Kwon, Andrew, Gergues, Mark M., Lalani, Lahin K., Fusi, Stefano, Kheirbek, Mazen A.

Issue&Volume: 2024-12-04

Abstract: Anhedonia, the diminished drive to seek, value, and learn about rewards, is a core feature of major depressive disorder1,2,3. The neural underpinnings of anhedonia and how this emotional state drives behaviour remain unclear. Here we investigated the neural code of anhedonia by taking advantage of the fact that when mice are exposed to traumatic social stress, susceptible animals become socially withdrawn and anhedonic, whereas others remain resilient. By performing high-density electrophysiology to record neural activity patterns in the basolateral amygdala (BLA) and ventral CA1 (vCA1), we identified neural signatures of susceptibility and resilience. When mice actively sought rewards, BLA activity in resilient mice showed robust discrimination between reward choices. By contrast, susceptible mice exhibited a rumination-like signature, in which BLA neurons encoded the intention to switch or stay on a previously chosen reward. Manipulation of vCA1 inputs to the BLA in susceptible mice rescued dysfunctional neural dynamics, amplified dynamics associated with resilience, and reversed anhedonic behaviour. Finally, when animals were at rest, the spontaneous BLA activity of susceptible mice showed a greater number of distinct neural population states. This spontaneous activity allowed us to decode group identity and to infer whether a mouse had a history of stress better than behavioural outcomes alone. This work reveals population-level neural dynamics that explain individual differences in responses to traumatic stress, and suggests that modulating vCA1–BLA inputs can enhance resilience by regulating these dynamics.

DOI: 10.1038/s41586-024-08241-y

Source: https://www.nature.com/articles/s41586-024-08241-y