Taiwanese scientists have discovered a new mechanism involved in the formation of fearful memories in mouse brains, which could point to new ways to treat post-traumatic stress disorder (PTSD) in the future. The study found that when mice experience fear, they activate a small group of nerve cells in a region of the brain called the amygdala. These cells work a bit like a brake pedal, helping to stop the mice from overreacting to fear. When the researchers blocked these nerve cells the mice exhibited more fear and froze in place for longer. Understanding how fearful memories are regulated and formed could point scientists towards a new target for treating conditions such as PTSD.
Journal/conference: Cell Reports
Link to research (DOI): 10.1016/j.celrep.2024.114468
Organisation/s: National Yang Ming Chiao Tung University, Taiwan
Funder: This work was supported
by grants to M.C. (AUFF NOVA 2016; PROMEMO – Center for Proteins
in Memory, a Center of Excellence funded by the Danish National Research
Foundation grant no. DNRF133; Independent Research Fund Denmark DFF-
37741); to F.F. (Austrian Science Fund grant no. I-2215); to C.-C.L. (Brain
Research Center, National Yang Ming Chiao Tung University from the Featured
Areas Research Center Program within the framework of the Higher Education
Sprout Project by the Ministry of Education in Taiwan, National Health
Research Institutes [NHRI-EX110-10814NI], and Ministry of Science and
Technology [108-2320-B-010-026-MY3; MOST 110-2321-B-010-006; 112-
Q11 2321-B-A49-009; 113-2321-B-A49-016 in Taiwan]); to W.-H.H. (Ministry of
Science and Technology, Taiwan, fellowship 110-2917-I-564-011); and to
K.-Y.W. (National Science and Technology Council fellowship 113-2917-I-
564-020).
Media release
From: Science Media Center Taiwan
Study in Mice May Help Mitigate Fear Memory and Lead to Potential PTSD Treatments.A newly discovered mechanism of fear memory formation in mouse brains may help reduce the negative impact of fear and provide new treatment methods for post-traumatic stress disorder (PTSD) in the future , according to a study published on August 5th in the open-access journal Cell Reports by Wen-Hsien Hou (侯文賢) from National Yang Ming Chiao Tung University, Taiwan, and colleagues.Recent literature has indicated that a group of nerve cells in the central amygdala regulates fear emotions. However, it was previously unclear whether specific nerve cells in this area are involved in forming fear memories and regulating responses to recalling these experiences. Most neuroscientists study how excitatory nerve cells in the brain handle memory storage and response, but they lack an understanding of the role of inhibitory nerve cells. This gap in knowledge makes it difficult to reveal how fear memories are regulated and how the brain reacts to them, such as maintaining an excitatory-inhibitory balance during the formation and recall of memories.In this study, researchers used mice as a model. They applied fear memory and learning tests to observe mice behavior before, during and after fear conditioning experiments, which paired a harmless sound with a slight electric shock to the foot.The study found that fear experiences activate a small group of inhibitory nerve cells in a specific brain region (the amygdala) in mice, preventing excessive reactions to fear memories.Using genetically modified mice, researchers marked these nerve cells activated by different fear experiences (mainly somatostatin-expressing nerve cells). Inhibiting these marked nerve cells resulted in the mice exhibiting more fear. “When these specific nerve cells were inhibited, the mice froze for a longer time when they anticipated an electric shock.” explained Dr. Hou, the first author and currently an Assistant Professor at Aarhus University.“These cells act like brakes, preventing excessive reactions to fear.” said Prof. Cheng-Chang Lien (連正章) who led the study.This study enhances our understanding of the neural basis of fear memory formation and may offer potential solutions for treating PTSD.The study has limitations. Although the brain structures of mice and humans are similar, there are differences in their neural circuits and connections. Further research is needed to determine if the central amygdala neurons regulate fear memories and responses in PTSD patients. Additionally, using advanced techniques like gene editing and chemogenetics in humans poses significant challenges for clinical development.This study was led by Prof. Lien from the College of Life Sciences at National Yang Ming Chiao Tung University in Taiwan, in collaboration with Prof. Marco Capogna from Aarhus University in Denmark and Prof. Francesco Ferraguti from the Medical University of Innsbruck in Austria.