As adults, we can usually recall little about events experienced during our early years. This phenomenon has been attributed to the restructuring of hippocampal circuitry in early postnatal life; however, whether the neuronal traces representing infant memories are permanently erased is unknown. Guskjolen et al. now show that infant memory traces are retained in a dormant state in the mouse dentate gyrus (DG) and that stimulation of these ‘silent engrams’ drives recall of lost memories.
Successful memory retrieval is thought to involve the reactivation of engrams active during memory formation. To investigate the apparent failure of this process in infant memory retrieval, the authors generated transgenic mice in which the neurons active during memory acquisition could be specifically and permanently ‘tagged’ with a light-activated ion channel, and used this system to investigate engram formation and reactivation following contextual fear conditioning (CFC).
Mice that underwent CFC as adults demonstrated long-lasting memory retention, freezing when re-exposed to the training context for at least 90 days after training. As expected, mice that were trained as infants (at postnatal day 17) exhibited rapid forgetting, with context-induced freezing abolished entirely within 90 days of training. However, when a laser was used to stimulate the DG neurons that had been tagged during training, context-induced freezing was reinstated in these mice, up to 90 days after training.
Next, the authors examined neuronal activity in regions downstream of the DG during light-stimulated recall. During the laser stimulation of the DG, they observed a specific reactivation of neurons that had been tagged during CFC acquisition in the hippocampal CA1 and CA3 regions and in several cortical regions. Thus, the reactivation of DG engrams activated downstream memory-associated neuronal ensembles.
the reactivation of DG engrams activated downstream memory-associated neuronal ensembles
These findings suggest that the engrams encoding memories that are formed early in life yet rapidly forgotten exist in a silent state in which they cannot be reactivated by natural recall cues.
Guskjolen, A. et al. Recovery of “lost” infant memories in mice. Curr. Biol. https://doi.org/10.1016/j.cub.2018.05.059 (2018)
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Tonegawa, S., Morrissey, M. W. & Kitamura, T. The role of engram cells in the systems consolidation of memory. Nat. Rev. Neurosci. https://doi.org/10.1038/s41583-018-0031-2 (2018)
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Whalley, K. Bringing back early memories. Nat Rev Neurosci 19, 517 (2018). https://doi.org/10.1038/s41583-018-0044-x