Synaptic tagging and capture underlie neuronal co-allocation and temporal association memory in behaving mice

Episodic memory has the ability to link distinct memories formed at temporal proximity (minutes-hours) into a coherent episodic representation. The neuronal mechanisms supporting such time associations remain however to be understood. The synaptic tagging and capture hypothesis (STC) provides a theoretical framework in which plasticity-related proteins produced for consolidating a memory trace at a synapse can potentially benefit to the consolidation of another trace at another synapse of the same neuron, thereby promoting neuronal co-allocations and temporal associations of memory traces. STC has however never been demonstrated in behaving animals, leaving its existence and functional relevance for memory formation unknown. We therefore investigated STC-like mechanisms in freely-behaving mice by recording hippocampal CA1 neurons during encoding and retrieval of distinct events. We found that reactivation of engram neurons at retrieval and the stability of place cells were strongly impaired by protein synthesis inhibition during encoding, but strikingly, were rescued in neurons that were coactive at another encoding close in time, having potentially benefitted from proteins produced at temporal proximity, as predicted by STC hypothesis. All our results together provide the first evidence of STC-like mechanisms in behaving animals and reveal an instrumental role of STC for time association of memory traces. ### Competing Interest Statement The authors have declared no competing interest.