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.

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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