A remote fear memory is a memory of traumatic events that occurred in the distant past — a few months to decades ago. A University of California, Riverside, mouse study published in Nature Neuroscience has now spelled out the fundamental mechanisms by which the brain consolidates remote fear memories.

The study demonstrates that remote fear memories formed in the distant past are permanently stored in connections between memory neurons in the prefrontal cortex, or PFC.

“It is the prefrontal memory circuits that are progressively strengthened after traumatic events and this strengthening plays a critical role in how fear memories mature to stabilized forms in the cerebral cortex for permanent storage,” said Jun-Hyeong Cho, an associate professor of molecular, cell and systems biology, who led the study. “Using a similar mechanism, other non-fear remote memories could also be permanently stored in the PFC.”

The brain uses distinct mechanisms to store recent versus remote fear memories. Previous studies have suggested that while the initial formation of fear memory involves the hippocampus, it progressively matures with time and becomes less dependent on the hippocampus. Much research now explains how recent fear memory is stored, but how the brain consolidates remote fear memories is not well understood.

The researchers focused on the PFC, a part of the cerebral cortex that has been implicated in remote memory consolidation in previous studies.

“We found a small group of nerve cells or neurons within the PFC, termed memory neurons, were active during the initial traumatic event and were reactivated during the recall of remote fear memory,” Cho said. “When we selectively inhibited these memory neurons in the PFC, it prevented the mice recalling remote but not recent fear memory, suggesting the critical role of PFC memory neurons in the recall of remote fear memories.”

In the experiments, the mice received an aversive stimulus in an environment called a context. They learned to associate the aversive stimulus with the context. When exposed to the same context a month later, the mice froze in response, indicating they could recall remote fear memories. The researchers showed that connections (synapses) between memory neurons in the PFC, termed prefrontal memory circuits, were gradually strengthened with time after fear learning, and such strengthening helped the PFC permanently store remote fear memories.

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