A protective mechanism discovered in the formation of fear memories could be the starting point for new therapies

Researchers from the Central Institute of Mental Health and the University of Heidelberg have identified a biological mechanism that regulates the strength of the memory of an aversive event. The results of their study offer new starting points for the development of therapies for psychiatric disorders.

Fear memories are crucial for an organism’s survival. They trigger appropriate reactions that enable adaptation to the environment. However, traumatic experiences can trigger strong memories of fear, which can lead to mental illnesses such as post-traumatic stress disorder (PTSD).

Researchers from the Central Institute of Mental Health (CIMH) and the University of Heidelberg have discovered a biological mechanism that may play a role in regulating resilience to adverse life events. The study is published in the journal Molecular Psychiatry.

PTSD is characterized, among other things, by disproportionate fear reactions to situations unrelated to the initial traumatic event. Therapies to treat these conditions include exposure therapy based on extinction of fear memories, but they often fail. The research group of Dr. Ana MM Oliveira, head of the Molecular and Cellular Cognition Research Department at CIMH, has studied the biological processes that can prevent the formation of strong fear memories.

Scientists have discovered that the formation of strong fear memories involves a unique molecular process that is not present in the consolidation of weak fear memories. In experiments on mice, they discovered that experiencing an aversive event results in two phases of high concentration of the Npas4 protein in the mouse brain.

In contrast, a mildly aversive event triggered only one phase. Interestingly, the authors also found that the second phase appears to function as an interruption that prevents very strong fear memories from forming. These results suggest that the brain is equipped with a mechanism that fine-tunes the strength of memory for an aversive event: a new discovery.

Specifically, the neuroscientists were able to show that blocking the second phase of Npas4 levels led to a stronger fear memory that was resistant to fear memory extinction and more likely to trigger disproportionate fear responses. Conversely, fear memory strength decreased when the second phase of Npas4 levels was artificially induced. Additionally, the mice showed weaker fear responses to situations unrelated to the initial traumatic experience.

The Npas4 protein plays a crucial role in communication between neurons. In their study, the researchers show that the biphasic increase in Npas4 protein levels in the brain after a traumatic event leads to a higher presence of the neurotransmitter GABA, responsible for dampening neuronal activity. Scientists suspect that this regulation of neuronal activity is the process by which Npas4 controls fear memory.

“In future studies, it will be important to understand why and how this intrinsic protective mechanism is sometimes bypassed and pathological memories still emerge,” explains Dr. Ana MM Oliveira. “Overall, our study reveals a molecular target that can be exploited for the development of novel therapies for psychiatric disorders.”

Provided by the Zentralinstitut für Seelische Gesundheit