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How the Brain Stores Remote Fear Memory – Neuroscience News

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Resume: Remote fear memories, or memories of trauma formed in the distant past, are stored in the connections between neurons in the prefrontal cortex.

Fountain: UCR

A remote fear memory is a memory of traumatic events that occurred in the distant past, a few months or decades ago. A mouse study from the University of California, Riverside, published in neuroscience of nature now he has explained the fundamental mechanisms by which the brain consolidates remote memories of fear.

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

The brain uses different mechanisms to store recent versus remote fear memories. Previous studies have suggested that while initial fear memory formation involves the hippocampus, it progressively matures over time and becomes less reliant 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, called memory neurons, that were active during the initial traumatic event and reactivated during remote fear memory recall,” Cho said. “When we selectively inhibited these memory neurons in the PFC, it prevented the mice from recalling remote but not recent fear memories, suggesting a pivotal role for 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 that they could recall remote fear memories.

The researchers showed that the connections (synapses) between memory neurons in the PFC, called prefrontal memory circuits, gradually strengthened over time after fear learning, and such strengthening helped the PFC to permanently store remote memories. from fear.

Next, to extinguish the remote fear memory in the mice, the researchers repeatedly exposed them to the same fear-predictive context but without the aversive stimulus. The result was a context-reduced fear response.

Fear memory neurons (red) among all neurons in the prefrontal cortex (blue). Credit: Cho Lab, UC Riverside.

“Interestingly, extinction of remote fear memory weakened prefrontal memory circuits that were previously strengthened to store remote fear memory,” Cho said. “In addition, other manipulations that blocked the strengthening of the PFC memory circuitry also prevented remote fear memory retrieval.”

Cho explained that a dysregulation of fear memory consolidation can lead to chronic maladaptive fear in PTSD, which affects around 6% of the population at some point in their lives.

“Given that PTSD patients suffer from fear memories formed in the distant past, our study provides important insight into the development of therapeutic strategies to suppress chronic fear in PTSD patients,” he said.

Next, Cho’s team plans to selectively weaken prefrontal memory circuits and examine whether this manipulation suppresses the retrieval of remote fear memories.

“We hope that the results will contribute to the development of more effective intervention in PTSD and other fear-related disorders,” Cho said.

Cho joined the studio with Ji-Hye Lee, Woong Bin Kim, and Eui Ho Park. The title of the article is “Neocortical Synaptic Engrams for Remote Contextual Memories”.

About this memory and neuroscience research news

Author: press office
Fountain: UCR
Contact: Press Office – UCR
Picture: Image is attributed to Cho lab, UC Riverside

See also

This shows the neurons in the brain stem.

original research: Open access.
“Neocortical Synaptic Engrams for Remote Contextual Memories” by Jun-Hyeong Cho et al. neuroscience of nature


Abstract

Neocortical synaptic engrams for remote contextual memories

Although the initial encoding of contextual memories involves strengthening of hippocampal circuitry, these memories progressively mature to stabilized forms in the neocortex and become less dependent on the hippocampus.

Although it has been proposed that long-term storage of contextual memories may involve lasting synaptic changes in neocortical circuits, synaptic substrates of remote contextual memories have been elusive.

Here we demonstrate that the consolidation of remote contextual fear memories in mice correlated with the progressive strengthening of excitatory connections between prefrontal cortical (PFC) engram neurons active during learning and reactivated during remote memory recall, while the extinction of remote memories weakened those synapses.

This synapse-specific plasticity was dependent on CREB and required sustained hippocampal signals, which the retrosplenial cortex could relay to PFCs. Furthermore, PFC engram neurons were strongly connected to other PFC neurons recruited during remote memory recall.

Our study suggests that progressive and synapse-specific strengthening of PFC circuits may contribute to the long-term storage of contextual memories.

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