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Internal representations about the external world can be driven by the external stimuli or can be internally generated in their absence. It has been a matter of debate whether novel stimuli from the external world are instructive over the brain network to create de novo representations or, alternatively, are selecting from existing pre-representations hosted in preconfigured brain networks. The hippocampus is a brain area necessary for normal internally generated spatial–temporal representations and its dysfunctions have resulted in anterograde amnesia, impaired imagining of new experiences, and hallucinations. The compressed temporal sequence of place cell activity in the rodent hippocampus serves as an animal model of internal representation of the external space. Based on our recent results on the phenomenon of novel place cell sequence preplay, we submit that the place cell sequence of a novel spatial experience is determined, in part, by a selection of a set of cellular firing sequences from a repertoire of existing temporal firing sequences in the hippocampal network. Conceptually, this indicates that novel stimuli from the external world select from their pre-representations rather than create de novo our internal representations of the world., RIKEN Brain Science Institute

Memories can be easily distorted, and a lack of relevant animal models has largely hindered our understanding of false-memory formation. Here, we first identified a population of cells in the dentate gyrus (DG) of the hippocampus that bear the engrams for a specific context; these cells were naturally activated during the encoding phase of fear conditioning and their artificial reactivation using optogenetics in an unrelated context was sufficient for inducing the fear memory specific to the conditioned context. In a further study, DG or CA1 neurons activated by exposure to a particular context were labelled with channelrhodopsin-2 (ChR2). These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context in which a foot shock was never delivered. The recall of this false memory was context specific, activated similar downstream regions engaged during natural fear-memory recall, and was also capable of driving an active fear response. Together, our data demonstrate that by substituting a natural conditioned stimulus with optogenetically reactivated DG cells that bear contextual memory engrams, it is possible to incept an internally and behaviourally represented false fear memory., National Institutes of Health (U.S.) (Grant R01-MH078821), National Institutes of Health (U.S.) (Grant P50-MH58880)