What is the neural code and statistical structure of neural states characterizing stress?
Our new work in Nature answers these questions and more. Thanks to my amazing co-first @fxia.bsky.social @stefanofusi.bsky.social @mazenkheirbek.bsky.social for precious guidance
www.nature.com/articles/s41...

A beautiful work with a wonderful team! A lot of new ideas and a huge number of elegant experiments

I am excited that my first Bluesky post is to share our new paper in @natureportfolio.bsky.social - "Understanding the neural code of stress to control anhedonia." With @fxia.bsky.social , @valeriafascianelli.bsky.social and @stefanofusi.bsky.social. www.nature.com/articles/s41...

Huge thanks to the dream team! Grateful for the support from @mazenkheirbek.bsky.social. Invaluable collaboration with my co-first @valeriafascianelli.bsky.social, and @stefanofusi.bsky.social. As well as Nina Vishwakarma, Frances Ghinger, Andrew Kwon, @markgergues.bsky.social, and Lahin Lalani!

11/ In summary, we identified novel signatures of stress resilience and susceptibility in the BLA, and could rescue these dysfunctional neural dynamics and anhedonia in susceptible mice by manipulating vCA1->BLA inputs.

10/ We found that spontaneous activity of susceptible mice had a greater number of distinct neural states in the BLA compared to controls. Notably, spontaneous activity was better at distinguishing between susceptible, resilient, and control mice than classic behavioral measures.

9/ Inspired by human studies, we next asked if “resting-state” population dynamics differed between susceptible, resilient, and control mice. We compared population geometry using PCA and used Hidden Markov Model with agglomerative clustering to identify distinct hidden states.

8/ Next, we modulated BLA activity by chemogenetic activation of the vCA1->BLA pathway. This rescued aberrant population dynamics and anhedonia-like behavior in susceptible mice, suggesting that targeting this pathway enhances BLA circuit function and rescues anhedonic behaviors.

7/ Are there neural representations that reflect the intention of mice to switch or stay on the same reward choice as the previous trial? Yes! But only in the BLA of susceptible mice, reminiscent of rumination-like states commonly observed in individuals with depression.

6/ We next examined the origins of anhedonic behavior in susceptible mice by analyzing the sequence of reward choices. We found that the choice sequence was Markovian, where the probability of choosing water or sucrose depends on the choice in the previous trial.

5/ We found enhanced reward choice (sucrose vs. water) representations at both single-neuron and population levels in the BLA of resilient mice as compared to controls and susceptible mice.

4/ Using behavioral measures, we identified mice that were resilient vs. susceptible to stress. As resilient mice showed stronger sucrose-seeking behavior, we first looked for specific adaptations in neural representations of reward-related information.

3/ We performed high-density Neuropixels recording in the basolateral amygdala (BLA) and ventral CA1 (vCA1) in mice following chronic social defeat stress while they performed a head-fixed sucrose preference task to assess anhedonia-like behavior.

2/ Here, we found that neural population dynamics in the amygdala, supported by the ventral hippocampus, can distinguish between resilient vs. susceptible mice following chronic stress during reward-guided decision making.

1/ It’s Saturday night, do you go out with friends or eat leftovers at home? If feeling down, you might choose the latter. Past trauma can shape our emotional states that bias our decisions. But what are the neural dynamics? And what makes some resilient and others susceptible?

Excited to share our new paper out now @natureportfolio.bsky.social, where we identified neural signatures of stress susceptibility and resilience in the amygdala-ventral hippocampal network to enable control of anhedonia!

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