Induction of activity synchronization among primed hippocampal neurons out of random dynamics is key for trace memory formation and retrieval

Memory is thought to be encoded by sparsely distributed neuronal ensembles in memory-related regions. However, it is unclear how memory-eligible neurons react during learning to encode trace fear memory and how they retrieve a memory. We implemented a fiber-optic confocal fluorescence endomicroscope to directly visualize calcium dynamics of hippocampal CA1 neurons in freely behaving mice subjected to trace fear conditioning. Here we report that the overall activity levels of CA1 neurons showed a right-skewed lognormal distribution, with a small portion of highly active neurons (termed Primed Neurons) filling the long-tail. Repetitive training induced Primed Neurons to shift from random activity to well-tuned synchronization. The emergence of activity synchronization coincided with the appearance of mouse freezing behaviors. In recall, a partial synchronization among the same subset of Primed Neurons was induced from random dynamics, which also coincided with mouse freezing behaviors. Additionally, training-induced synchronization facilitated robust calcium entry into Primed Neurons. In contrast, most CA1 neurons did not respond to tone and foot shock throughout the training and recall cycles. In conclusion, Primed Neurons are preferably recruited to encode trace fear memory and induction of activity synchronization among Primed Neurons out of random dynamics is critical for trace memory formation and retrieval.