Stress is considered a risk factor for mood disorders. The hippocampus is thought to negatively regulate the stress response and to mediate various cognitive and mnemonic aspects of stress-induced impairments, although the neuronal pathways supporting behavioural improvements are largely unknown.

In this report, researchers acutely rescue stress-induced depression-related behaviours in mice by optogenetically reactivating dentate gyrus cells that were previously active during a positive experience. A brain-wide histological investigation, coupled with pharmacological and projection-specific optogenetic blockade experiments, identified glutamatergic activity in the hippocampus–amygdala–nucleus-accumbens pathway as a candidate circuit supporting the acute rescue.

Chronically reactivating hippocampal cells associated with a positive memory resulted in the rescue of stress-induced behavioural impairments and neurogenesis at time points beyond the light stimulation. The authors suggest that activating positive memories artificially is sufficient to suppress depression-like behaviours and point to dentate gyrus engram cells as potential therapeutic nodes for intervention of maladaptive behavioural states.

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Ramirez S, Liu X, MacDonald CJ, Moffa A, Zhou J, Redondo RL, Tonegawa S: Activating positive memory engrams suppresses depression-like behavior. Nature 522: 335–339 (2015); doi:10.1038/nature14514.
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http://www.nature.com/nature/journal/v522/n7556/full/nature14514.html