Neural Pathway Identified in Formation of Fear Memories from Psychological Threats

Fri 16th May, 2025

Recent research conducted by a team at the Korea Advanced Institute of Science and Technology (KAIST) has unveiled a crucial neural pathway involved in the formation of fear memories triggered by psychological threats. This groundbreaking discovery could pave the way for innovative treatments for mental health disorders such as post-traumatic stress disorder (PTSD), anxiety, and depression, which often arise from traumatic experiences rather than direct physical harm.

The study, published in the journal Science Advances, highlights the significance of the pIC-PBN circuit, a neural pathway that operates in the absence of physical pain to process fear memories. Traditionally, the parabrachial nucleus (PBN) has been associated with pain processing; however, this new research reveals its role in responding to non-painful psychological stimuli, fundamentally altering our understanding of how fear is processed in the brain.

Fear memories typically develop following exposure to threatening situations, including natural disasters and violent encounters. When these memories become distorted or excessive, they can lead to severe mental health issues. Despite this, the mechanisms that underpin fear memory formation linked to psychological threats have remained poorly understood until now.

Led by Professor Jin-Hee Han, the research team utilized a novel experimental model that involved exposing mice to visual stimuli that simulate the threat of an approaching predator. This method allowed the researchers to demonstrate that fear memories can be formed based solely on psychological threats, without the need for any physical pain.

Through the use of advanced chemogenetic and optogenetic techniques, the team effectively controlled neuronal activity and confirmed the essential role of the lateral parabrachial nucleus in the formation of fear memories in response to visual threats. They traced the signals back to the posterior insular cortex (pIC), a brain region known for processing negative emotions and pain, revealing a direct connection between emotional distress and fear memory formation.

Furthermore, the study indicated that inhibiting the pIC-PBN circuit significantly reduced the formation of fear memories in response to visual stimuli, while artificial activation of this circuit was sufficient to induce fear memory formation. This suggests that emotional distress and physical pain are processed through distinct neural circuits.

The implications of these findings are profound, as they establish a dedicated pathway for the transmission of psychological threat information that could inform targeted therapeutic strategies for mental health conditions. By understanding the neural underpinnings of how fear memories are created, researchers can begin to develop more effective treatments that address the root causes of these conditions rather than merely alleviating symptoms.

As mental health issues continue to rise globally, the identification of this neural pathway offers hope for more precise and effective interventions, potentially transforming the landscape of mental health treatment in the future.


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