Cortical Representations Are Reinstated By The Hippocampus During Memory Retrieval

SUMMARY The hippocampus is assumed to retrieve memory by reinstating patterns of cortical activity that were observed during learning. To test this idea, we monitored the activity of individual cortical neurons while simultaneously inactivating the hippocampus. Neuronsthatwereactiveduringcontextfearconditioning were tagged with the long-lasting fluorescent protein H2B-GFPandthelight-activatedprotonpumpArchT. These proteins allowed us to identify encoding neurons several days after learning and silence them with laser stimulation. When tagged CA1 cells were silenced, we found that memory retrieval was impaired and representations in the cortex (entorhinal, retrosplenial, perirhinal) and the amygdala could not be reactivated. Importantly, hippocampal inactivation did not alter the total amount of activity in most brain regions. Instead, it selectively prevented neuronsthatwereactiveduringlearningfrombeingreactivatedduringretrieval.Thesedataprovidefunctional evidence that the hippocampus reactivates specific memory representations during retrieval.