The term “remote fear memory” refers to a recollection of a terrifying incident that happened a long time ago, anything from a few months to many decades ago. Now, a study on mice done at the University of California, Riverside and published in Nature Neuroscience has shown how the brain makes long-term fear memories.
The study shows that fear memories from a long time ago are stored permanently in the connections between memory neurons in the PFC, or prefrontal cortex.
According to the study’s lead author, associate professor of molecular, cell, and systems biology Jun-Hyeong Cho, “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.”
Other non-fear remote memories might be permanently retained in the PFC via a similar manner.
The brain uses different ways to store recent and old fear memories. Previous research has revealed that although the hippocampus is involved in the early development of fear memory, it gradually develops with time and becomes less reliant on the hippocampus. Although the processes by which the brain archives fresh fear experiences have been thoroughly investigated, it remains unclear how the brain stores and consolidates more distant fear experiences.
The researchers focused on the prefrontal cortex (PFC), which is a part of the brain that has been linked to the consolidation of long-term memories 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 explains. “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.”
The mice were exposed to painful stimuli in an experimental setting. They learned to link the unpleasant stimulus to the situation. When the mice were put in the same situation a month later, they froze, which showed that they could remember past fears. The researchers demonstrated that connections (synapses) between memory neurons in the PFC, referred to as prefrontal memory circuits, steadily strengthened over time following fear learning, allowing the PFC to permanently retain distant fear memories.
Next, the researchers exposed the mice over and over again to the same fear-predicting context, but without the aversive stimulus. This erased the mice’s memory of the fear from a long time ago. The outcome was a diminished fear reaction to the environment.
“Interestingly, the extinction of remote fear memory weakened the prefrontal memory circuits that were previously strengthened to store the remote fear memory,” Cho adds. “Moreover, other manipulations that blocked the strengthening of the PFC memory circuits also prevented the recall of remote fear memory.”
Cho said that in PTSD, which affects roughly 6% of the population at some time in their life, a dysregulation of fear memory consolidation may result in persistent, maladaptive fear.
“Considering that PTSD patients suffer from fear memories formed in the distant past, our study provides an important insight into developing therapeutic strategies to suppress chronic fear in PTSD patients,” he adds.
Next, Cho’s team wants to weaken some of the prefrontal memory circuits and see if this stops people from remembering distant fear memories.
“We expect the results will contribute to developing a more effective intervention in PTSD and other fear-related disorders,” Cho adds.
Image Credit: Getty
