Mouse study could lead to novel therapies for people with PTSD – Zoo House News

Mouse study could lead to novel therapies for people with PTSD – Zoo House News

  • Science
  • January 1, 2023
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A distant fear memory is a memory of traumatic events that happened in the distant past—a few months to decades ago. A mouse study from the University of California, Riverside, published in Nature Neuroscience, has now revealed the basic mechanisms by which the brain consolidates distant fear memories.

The study shows that distant 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 increasingly strengthened after traumatic events, and this strengthening plays a crucial 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 remote memories could also be permanently stored in the PFC without fear.”

The brain uses different mechanisms to store current and distant fear memories. Previous studies have shown that while the initial formation of fear memory involves the hippocampus, over time it matures and becomes less dependent on the hippocampus. Much research now explains how current fear memories are stored, but how the brain consolidates distant fear memories is not well understood.

Researchers focused on the PFC, a part of the cerebral cortex that has been implicated in long-distance memory consolidation in previous studies.

“We found a small cluster of nerve cells, or neurons, within the PFC, called memory neurons, that were active during the initial traumatic event and reactivated during the retrieval of distant fear memories,” Cho said. “When we selectively inhibited these memory neurons in the PFC, this prevented the mice from recalling distant but not recent fear memories, suggesting the critical role of PFC memory neurons in recalling distant fear memories.”

In the experiments, the 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, suggesting they could recall distant fear memories. The researchers showed that connections (synapses) between memory neurons in the PFC, called prefrontal memory circuits, gradually strengthened over time after fear learning, and such reinforcement helped the PFC permanently store distant fear memories.

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

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

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

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

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

“We expect the results will help develop a more effective intervention for PTSD and other anxiety-related disorders,” Cho said.

The study was supported 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.

story source:

Materials provided by University of California – Riverside. Originally written by Iqbal Pittalwala. Note: Content can be edited for style and length.

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