Systems consolidation induces multiple memory engrams for a flexible recall strategy in observational fear memory in male mice.

Observers learn to fear the context in which they witnessed a demonstrator's aversive experience, called observational contextual fear conditioning (CFC). The neural mechanisms governing whether recall of the observational CFC memory occurs from the observer's own or from the demonstrator's point of view remain unclear. Here, we show in male mice that recent observational CFC memory is recalled in the observer's context only, but remote memory is recalled in both observer and demonstrator contexts. Recall of recent memory in the observer's context requires dorsal hippocampus activity, while recall of remote memory in both contexts requires the medial prefrontal cortex (mPFC)-basolateral amygdala pathway. Although mPFC neurons activated by observational CFC are involved in remote recall in both contexts, distinct mPFC subpopulations regulate remote recall in each context. Our data provide insights into a flexible recall strategy and the functional reorganization of circuits and memory engram cells underlying observational CFC memory.