Nature—挫商高不高，多巴胺说了算；抗压能力强不强，多巴胺说了算：VTA-NAc环路是关键！！

中文摘要

慢性压力可能会对一些人造成持续的不良后果，但其他人对相同的压力却能产生抵抗。在压力应激结束以后，压力易感和压力抵抗的人在中脑-边缘系统多巴胺（DA）神经元的内在特性上表现出差异。然而，多巴胺和压力下的行为及个体抵抗力差异之间的因果关系尚不清楚。在这项研究中，研究人员记录了在社交失败期间，小鼠的行为和投射到伏隔核（NAc）（发出奖励的信号）和尾部纹状体（TS）（发出威胁的信号）的DA神经元的活动。有监督和无监督的行为量化表明，在应激期间，压力抵抗和压力易感小鼠使用不同的行为策略，其在NAc（而不是TS）的DA神经元终末有不同的活动模式。在神经机制层面上，压力抵抗的小鼠在侵略者附近有更强的DA神经元活动，包括在开始反击时也是如此。相反，压力易感小鼠在攻击失效和逃跑开始时具有更强DA神经元活动。通过实时行为分类方法，研究人员还在小鼠挫败（随机-开环刺激）或执行特定行为时使用光遗传学手段特异性激活投射到NAc的 DA神经元。开环反击刺激或定时激活都可增强小鼠对压力的抵抗力，并在失败过程中重新组织行为，形成与抵抗力相关的模式。总之，他们的研究结果揭示了DA神经元活动、抵抗力和压力抵抗相关行为之间的联系。

英文摘要

Chronic stress can have lasting adverse consequences in some individuals, yet others are resilient to the same stressor. Susceptible and resilient individuals exhibit differences in the intrinsic properties of mesolimbic dopamine (DA) neurons after the stressful experience is over. However, the causal links between DA, behaviour during stress and individual differences in resilience are unknown. Here we recorded behaviour in mice simultaneously with DA neuron activity in projections to the nucleus accumbens (NAc) (which signals reward) and the tail striatum (TS) (which signals threat) during social defeat. Supervised and unsupervised behavioural quantification revealed that during stress, resilient and susceptible mice use different behavioural strategies and have distinct activity patterns in DA terminals in the NAc (but not the TS). Neurally, resilient mice have greater activity near the aggressor, including at the onset of fighting back. Conversely, susceptible mice have greater activity at the offset of attacks and onset of fleeing. We also performed optogenetic stimulation of NAc-projecting DA neurons in open loop (randomly timed) during defeat or timed to specific behaviours using real-time behavioural classification. Both open-loop and fighting-back-timed activation promoted resilience and reorganized behaviour during defeat towards resilience-associated patterns. Together, these data provide a link between DA neural activity, resilience and resilience-associated behaviour during the experience of stress.

参考文献：Behavioural and dopaminergic signatures of resilience. Nature. 2022 Oct 19. doi: 10.1038/s41586-022-05328-2. Online ahead of print.

微信视频预览查看