Brain+circuit
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Decoding Fear: KAIST Identifies An Affective Brain Circuit Crucial for Fear Memory Formation by Non-nociceptive Threat Stimulus
Fear memories can form in the brain following exposure to threatening situations such as natural disasters, accidents, or violence. When these memories become excessive or distorted, they can lead to severe mental health disorders, including post-traumatic stress disorder (PTSD), anxiety disorders, and depression. However, the mechanisms underlying fear memory formation triggered by affective pain rather than direct physical pain have remained largely unexplored – until now.
A KAIST research team has identified, for the first time, a brain circuit specifically responsible for forming fear memories in the absence of physical pain, marking a significant advance in understanding how psychological distress is processed and drives fear memory formation in the brain. This discovery opens the door to the development of targeted treatments for trauma-related conditions by addressing the underlying neural pathways.
< Photo 1. (from left) Professor Jin-Hee Han, Dr. Junho Han and Ph.D. Candidate Boin Suh of the Department of Biological Sciences >
KAIST (President Kwang-Hyung Lee) announced on May 15th that the research team led by Professor Jin-Hee Han in the Department of Biological Sciences has identified the pIC-PBN circuit*, a key neural pathway involved in forming fear memories triggered by psychological threats in the absence of sensory pain. This groundbreaking work was conducted through experiments with mice.*pIC–PBN circuit: A newly identified descending neural pathway from the posterior insular cortex (pIC) to the parabrachial nucleus (PBN), specialized for transmitting psychological threat information.
Traditionally, the lateral parabrachial nucleus (PBN) has been recognized as a critical part of the ascending pain pathway, receiving pain signals from the spinal cord. However, this study reveals a previously unknown role for the PBN in processing fear induced by non-painful psychological stimuli, fundamentally changing our understanding of its function in the brain.
This work is considered the first experimental evidence that 'emotional distress' and 'physical pain' are processed through different neural circuits to form fear memories, making it a significant contribution to the field of neuroscience. It clearly demonstrates the existence of a dedicated pathway (pIC-PBN) for transmitting emotional distress.
The study's first author, Dr. Junho Han, shared the personal motivation behind this research: “Our dog, Lego, is afraid of motorcycles. He never actually crashed into one, but ever since having a traumatizing event of having a motorbike almost run into him, just hearing the sound now triggers a fearful response. Humans react similarly – even if you didn’t have a personal experience of being involved in an accident, a near-miss or exposure to alarming media can create lasting fear memories, which may eventually lead to PTSD.”
He continued, “Until now, fear memory research has mainly relied on experimental models involving physical pain. However, much of real-world human fears arise from psychological threats, rather than from direct physical harm. Despite this, little was known about the brain circuits responsible for processing these psychological threats that can drive fear memory formation.”
To investigate this, the research team developed a novel fear conditioning model that utilizes visual threat stimuli instead of electrical shocks. In this model, mice were exposed to a rapidly expanding visual disk on a ceiling screen, simulating the threat of an approaching predator. This approach allowed the team to demonstrate that fear memories can form in response to a non-nociceptive, psychological threat alone, without the need for physical pain.
< Figure 1. Artificial activation of the posterior insular cortex (pIC) to lateral parabrachial nucleus (PBN) neural circuit induces anxiety-like behaviors and fear memory formation in mice. >
Using advanced chemogenetic and optogenetic techniques, the team precisely controlled neuronal activity, revealing that the lateral parabrachial nucleus (PBN) is essential to form fear memories in response to visual threats. They further traced the origin of these signals to the posterior insular cortex (pIC), a region known to process negative emotions and pain, confirming a direct connection between the two areas.
The study also showed that inhibiting the pIC–PBN circuit significantly reduced fear memory formation in response to visual threats, without affecting innate fear responses or physical pain-based learning. Conversely, artificially activating this circuit alone was sufficient to drive fear memory formation, confirming its role as a key pathway for processing psychological threat information.
< Figure 2. Schematic diagram of brain neural circuits transmitting emotional & physical pain threat signals. Visual threat stimuli do not involve physical pain but can create an anxious state and form fear memory through the affective pain signaling pathway. >
Professor Jin-Hee Han commented, “This study lays an important foundation for understanding how emotional distress-based mental disorders, such as PTSD, panic disorder, and anxiety disorder, develop, and opens new possibilities for targeted treatment approaches.”
The findings, authored by Dr. Junho Han (first author), Ph.D. candidate Boin Suh (second author), and Dr. Jin-Hee Han (corresponding author) of the Department of Biological Sciences, were published online in the international journal Science Advances on May 9, 2025.※ Paper Title: A top-down insular cortex circuit crucial for non-nociceptive fear learning. Science Advances (https://doi.org/10.1101/2024.10.14.618356)※ Author Information: Junho Han (first author), Boin Suh (second author), and Jin-Hee Han (corresponding author)
This research was supported by grants from the National Research Foundation of Korea (NRF-2022M3E5E8081183 and NRF-2017M3C7A1031322).
2025.05.15 View 561 -
Scientists Develop Wireless Networks that Allow Brain Circuits to Be Controlled Remotely through the Internet
Wireless implantable devices and IoT could manipulate the brains of animals from anywhere around the world due to their minimalistic hardware, low setup cost, ease of use, and customizable versatility
A new study shows that researchers can remotely control the brain circuits of numerous animals simultaneously and independently through the internet. The scientists believe this newly developed technology can speed up brain research and various neuroscience studies to uncover basic brain functions as well as the underpinnings of various neuropsychiatric and neurological disorders.
A multidisciplinary team of researchers at KAIST, Washington University in St. Louis, and the University of Colorado, Boulder, created a wireless ecosystem with its own wireless implantable devices and Internet of Things (IoT) infrastructure to enable high-throughput neuroscience experiments over the internet. This innovative technology could enable scientists to manipulate the brains of animals from anywhere around the world. The study was published in the journal Nature Biomedical Engineering on November 25
“This novel technology is highly versatile and adaptive. It can remotely control numerous neural implants and laboratory tools in real-time or in a scheduled way without direct human interactions,” said Professor Jae-Woong Jeong of the School of Electrical Engineering at KAIST and a senior author of the study. “These wireless neural devices and equipment integrated with IoT technology have enormous potential for science and medicine.”
The wireless ecosystem only requires a mini-computer that can be purchased for under $45, which connects to the internet and communicates with wireless multifunctional brain probes or other types of conventional laboratory equipment using IoT control modules. By optimally integrating the versatility and modular construction of both unique IoT hardware and software within a single ecosystem, this wireless technology offers new applications that have not been demonstrated before by a single standalone technology. This includes, but is not limited to minimalistic hardware, global remote access, selective and scheduled experiments, customizable automation, and high-throughput scalability.
“As long as researchers have internet access, they are able to trigger, customize, stop, validate, and store the outcomes of large experiments at any time and from anywhere in the world. They can remotely perform large-scale neuroscience experiments in animals deployed in multiple countries,” said one of the lead authors, Dr. Raza Qazi, a researcher with KAIST and the University of Colorado, Boulder. “The low cost of this system allows it to be easily adopted and can further fuel innovation across many laboratories,” Dr. Qazi added.
One of the significant advantages of this IoT neurotechnology is its ability to be mass deployed across the globe due to its minimalistic hardware, low setup cost, ease of use, and customizable versatility. Scientists across the world can quickly implement this technology within their existing laboratories with minimal budget concerns to achieve globally remote access, scalable experimental automation, or both, thus potentially reducing the time needed to unravel various neuroscientific challenges such as those associated with intractable neurological conditions.
Another senior author on the study, Professor Jordan McCall from the Department of Anesthesiology and Center for Clinical Pharmacology at Washington University in St. Louis, said this technology has the potential to change how basic neuroscience studies are performed. “One of the biggest limitations when trying to understand how the mammalian brain works is that we have to study these functions in unnatural conditions. This technology brings us one step closer to performing important studies without direct human interaction with the study subjects.”
The ability to remotely schedule experiments moves toward automating these types of experiments. Dr. Kyle Parker, an instructor at Washington University in St. Louis and another lead author on the study added, “This experimental automation can potentially help us reduce the number of animals used in biomedical research by reducing the variability introduced by various experimenters. This is especially important given our moral imperative to seek research designs that enable this reduction.”
The researchers believe this wireless technology may open new opportunities for many applications including brain research, pharmaceuticals, and telemedicine to treat diseases in the brain and other organs remotely. This remote automation technology could become even more valuable when many labs need to shut down, such as during the height of the COVID-19 pandemic.
This work was supported by grants from the KAIST Global Singularity Research Program, the National Research Foundation of Korea, the United States National Institute of Health, and Oak Ridge Associated Universities.
-PublicationRaza Qazi, Kyle Parker, Choong Yeon Kim, Jordan McCall, Jae-Woong Jeong et al. “Scalable and modular wireless-network infrastructure for large-scale behavioral neuroscience,” Nature Biomedical Engineering, November 25 2021 (doi.org/10.1038/s41551-021-00814-w)
-ProfileProfessor Jae-Woong JeongBio-Integrated Electronics and Systems LabSchool of Electrical EngineeringKAIST
2021.11.29 View 15158