Irreplaceability of Neuronal Ensembles after Memory Allocation

• Inhibiting learning-activated neural ensembles impairs memory retrieval
• Inhibiting neural ensembles activated during learning impairs relearning
• Inhibiting neural ensembles for a specific memory does not hinder distinct learning

SummaryLesion studies suggest that an alternative system can compensate for damage to the primary region employed when animals acquire a memory. However, it is unclear whether functional compensation occurs at the cellular ensemble level. Here, we inhibited the activities of a specific subset of neurons activated during initial learning by utilizing a transgenic mouse that expresses tetanus toxin (TeNT) under the control of the c-fos promoter. Notably, suppression interfered with relearning while sparing the ability to acquire and express fear memory for a distinct context. These results suggest that the activity of the initial ensemble is preferentially dedicated to the same learning and that it is not replaceable once it is allocated. Our results provide substantial insights into the machinery underlying how the brain allocates individual memories to discrete neuronal ensembles and how it ensures that repetitive learning strengthens memory by reactivating the same neuronal ensembles.

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