Erasable hippocampal neural signatures predict memory discrimination

Memories involving the hippocampus can take several days to consolidate, challenging efforts to uncover the neuronal signatures underlying this process. Here, we use calcium imaging in freely moving mice to track the hippocampal dynamics underlying memory consolidation across a 10-day contextual fear conditioning task. We find two neural signatures that emerge following learning and predict memory performance: context-specific place field remapping and coordinated neural activity prior to memory recall (freezing). To test whether these signatures support memory consolidation, we pharmacologically induced amnesia in separate mice by administering anisomycin, a protein synthesis inhibitor, immediately following learning. We find that anisomycin paradoxically accelerates cell turnover. Anisomycin also arrests learning-related remapping and blocks coordinated activity predictive of memory-related freezing behavior, effects that are likewise absent in untreated mice that exhibit poor memory expression. We conclude that context-specific place field remapping and the development of coordinated ensemble activity underlie contextual memory consolidation.