Can recalling positive memories alleviate depression? Susumu Tonegawa and colleagues addressed this question in mice using optogenetically labelled specific hippocampal memory engrams associated with a positive, neutral or negative experience. The memories could then be artificially activated with light at a later time. Acute reactivation of the positive engram was found to suppress depression-like behaviour in mice exposed to chronic stress, an effect mediated by the hippocampus–amygdala–nucleus-accumbens pathway. Importantly, chronic reactivation of the positive engram also prevented depression-like behaviour in stressed mice even after the reactivation had finished, indicating that the antidepressant effect is not dependent on real-time artificial activation of the engram. The authors suggest that direct activation of hippocampal dentate gyrus engram cells associated with a positive memory may offer a potential therapeutic node for alleviating a subset of depression-related behaviours, although at this stage it is not clear how these findings may translate into humans.
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