Zhukovskaya Anna, Zimmerman Christopher A, Willmore Lindsay, Pan-Vazquez Alejandro, Janarthanan Sanjeev R, Lynch Laura A, Falkner Annegret L, Witten Ilana B
Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.
Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.
Neuron. 2024 Dec 4;112(23):3940-3956.e10. doi: 10.1016/j.neuron.2024.09.009. Epub 2024 Oct 10.
Some individuals are susceptible to chronic stress, and others are more resilient. While many brain regions implicated in learning are dysregulated after stress, little is known about whether and how neural teaching signals during stress differ between susceptible and resilient individuals. Here, we seek to determine if activity in the lateral habenula (LHb), which encodes a negative teaching signal, differs between susceptible and resilient mice during stress to produce different outcomes. After (but not before) chronic social defeat stress, the LHb is active when susceptible mice are in proximity of the aggressor strain. During stress, activity is higher in susceptible mice during aggressor interactions, and activation biases mice toward susceptibility. This manipulation generates a persistent and widespread increase in the balance of subcortical vs. cortical activity in susceptible mice. Taken together, our results indicate that heightened activity in the LHb during stress produces lasting brainwide and behavioral substrates of susceptibility.
一些个体易受慢性应激影响，而另一些个体则更具恢复力。虽然许多与学习相关的脑区在应激后会出现失调，但对于应激期间易感个体和恢复力强的个体之间神经教学信号是否以及如何不同，我们知之甚少。在这里，我们试图确定编码负性教学信号的外侧缰核（LHb）的活动在应激期间易感小鼠和恢复力强的小鼠之间是否存在差异，从而产生不同的结果。在慢性社会挫败应激之后（而非之前），当易感小鼠靠近攻击菌株时，LHb会被激活。在应激期间，在与攻击者互动时，易感小鼠的活动更高，并且这种激活使小鼠倾向于易感性。这种操作在易感小鼠中导致皮层下与皮层活动平衡的持续广泛增加。综上所述，我们的结果表明，应激期间LHb活动增强会产生持久的全脑范围和行为易感性的基础。
