Check out our new preprint on neural signatures of stress susceptibility and resilience in the amygdala-ventral hippocampal network! https://t.co/sYSA8K5dkP Thread below 👇
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1/ It’s Saturday night, do you choose going out with friends or eating leftovers at home? Feeling low, you might choose leftovers. Past trauma changes our emotional states that bias our decisions, but what are the neural dynamics? What makes some resilient and others susceptible?
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2/ Here, we found that neural population dynamics in the amygdala with support from the ventral hippocampus can distinguish between resilient vs. susceptible mice following chronic stress during reward-guided decision making.
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3/ We recorded single neuron activity 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.
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4/ Using behavioral measures, we identified those that were resilient vs. susceptible to stress. As resilient mice showed more robust sucrose-seeking behavior, we first looked for specific adaptations in neural representations of reward-related information.
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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.
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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.
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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.
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8/ 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.
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9/ We found that spontaneous activity in BLA of susceptible mice was higher dimensional than controls, reflecting the exploration of a larger number of distinct neural states. Moreover, spontaneous activity can distinguish between susceptible, resilient, and control mice!
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10/ Finally, we rescued the aberrant population dynamics and behavioral signatures of anhedonia in susceptible mice via chemogenetic activation of the vCA1->BLA pathway, suggesting that targeting this pathway can enhance BLA circuit function and rescue anhedonic behaviors.
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11/ In summary, here 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.
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end/ Huge thanks to everyone who contributed to this massive endeavor! Expert guidance and tremendous support from @mazen_kheirbek. Indispensable collaboration with my co-first @VFascianelli, and @StefanoFusi2. As well as amazing RAs @nineuron and Frances Ghinger!
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@_fxia Sensational work Frances! I am so grateful to have seen the story mature over a few seminars… fantastic stuff! Excited to see what’s next
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