A distant fear memory is a memory of traumatic events that occurred in the distant past –; a few months to a few decades ago. A mouse study from the University of California, Riverside, published in Natural neuroscience has now clarified the fundamental mechanisms by which the brain consolidates distant fear memories.
The study demonstrates that remote fear memories formed in the distant past are permanently stored in the connections between memory neurons in the prefrontal cortex, or PFC.
It is the prefrontal memory circuits that are progressively reinforced after traumatic events and this reinforcement plays a critical role in how fear memories mature into stabilized forms in the cerebral cortex for permanent storage. Using a similar mechanism, other fearless remote memories could also be permanently stored in the PFC. »
Jun-Hyeong Cho, Associate Professor of Molecular, Cellular and Systems Biology, Study Leader
The brain uses distinct mechanisms to store recent and distant fear memories. Previous studies have suggested that while the initial formation of fear memory involves the hippocampus, it gradually matures over 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 that a small group of nerve cells or neurons within the PFC, called memory neurons, were active during the initial traumatic event and were reactivated upon remote fear memory recall,” Cho said. “When we selectively inhibited these memory neurons in the PFC, it prevented the mice from recalling distant but not recent fear memory, suggesting the critical role of PFC memory neurons in recalling memories of fear. remote fear. »
In the experiments, mice received an aversive stimulus in an environment called 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 that they could recall distant fear memories. The researchers showed that the connections (synapses) between memory neurons in the PFC, called prefrontal memory circuits, were progressively reinforced over time after fear learning, and such reinforcement helped the PFC to store in permanence of remote fear memories.
Then, to turn off remote fear memory in the mice, the researchers repeatedly exposed the mice to the same predictive fear context but without the aversive stimulus. The result was a context-reduced fear response.
“Interestingly, the extinction of remote fear memory weakened prefrontal memory circuitry that was previously enhanced to store remote fear memory,” Cho said. “Furthermore, other manipulations that blocked reinforcement of PFC memory circuitry also prevented remote fear memory recall. »
Cho explained that a dysregulation of fear memory consolidation can lead to chronic maladaptive fear in PTSD, which affects about 6% of the population at some point in their lives.
“Given that patients with PTSD suffer from memories of fear formed in the distant past, our study provides important insight into the development of therapeutic strategies to suppress chronic fear in patients with PTSD,” he said. .
Next, Cho’s team plans to selectively weaken prefrontal memory circuitry and examine whether this manipulation suppresses remote fear memory recall.
“We hope the results will help develop a more effective intervention in PTSD and other fear-related disorders,” Cho said.
The study was funded by grants from the National Institutes of Mental Health.
Cho was joined in the study by Ji-Hye Lee, Woong Bin Kim and Eui Ho Park.