A recent study has identified the brain’s mechanism for distinguishing between current, real dangers and memories of past threats. This discovery, published in Nature, has important implications for our understanding of post-traumatic stress disorder (PTSD).
Professor Eric Klann, the senior author and Director of the Neuroscience Center at New York University, explained, “Traumatic memories can last a long time. But we are able to selectively use these memories to predict and respond to future dangers, while also recognizing when there is no threat. This ability is especially critical for survival in uncertain environments.”
Prerana Shrestha, a postdoctoral researcher at the NYU Neuroscience Center and co-author of the study, added, “This has significant implications for memory disorders like PTSD, where patients struggle to differentiate between past and present threats.”
The research, which also involved scientists from Rockefeller University and McGill University, focused on the neural processes in mice that help them make this crucial distinction.
In uncertain environments, it is vital for animals to learn how to identify and respond appropriately to threats. However, uncertain environments also provide cues that predict safety—or at least the absence of danger. As a result, animals must respond to threat cues with defensive behaviors, but they should also recognize safe cues and cease their defensive responses, returning to normal behavior.
In this study, the researchers aimed to identify the molecular or cellular substrates that are responsible for storing long-term memories related to threats and safety cues.
For a long time, the amygdala has been known to play a key role in processing and storing emotionally relevant information. However, much less is understood about the cellular processes and mechanisms underlying this activity. It’s well established that the formation and consolidation of long-term memories are linked to changes in the protein landscape of cells—these changes capture important features of events, partly through the synthesis of new proteins.
In their new work, the researchers sought to understand these processes better by disrupting key steps in protein synthesis in specific cell types. This approach allowed them to identify the critical players involved.
The researchers focused on two protein complexes essential for synthesizing new proteins. The first contains eIF2, which adds amino acids to proteins as they are synthesized. The second contains eIF4E, which binds to the "cap" of messenger RNA (mRNA), which is necessary for translating it into protein.
Interestingly, they found that protein synthesis in certain inhibitory neurons of the amygdala was crucial for storing memories related to threat cues. On the other hand, protein synthesis in neurons expressing PKCδ was essential for storing memories related to safety cues.
Previously, it had been shown that the activity of these specific neuron populations is involved in processing threat-related cues. However, this is the first study to link the necessity of new protein synthesis in these neurons with the stabilization of long-term emotional memories.
This groundbreaking research provides new insights into how the brain distinguishes between past and present threats and how it stores memories related to both danger and safety. Understanding these processes could have significant implications for disorders like PTSD, where patients struggle to separate past traumatic events from current realities.
