2024-03-14 カリフォルニア大学サンディエゴ校(UCSD)
New research published in Science identifies the brain biochemistry and neural circuitry that cause generalized fear experiences. Here, neurons are shown in cyan and retrograde tracers shown in yellow and magenta. Spitzer Lab, UC San Diego
<関連情報>
- https://today.ucsd.edu/story/how-fear-unfolds-inside-our-brains
- https://www.science.org/doi/10.1126/science.adj5996
急性ストレス後の全般性恐怖は神経細胞共伝達物質の同一性の変化によって引き起こされる Generalized fear after acute stress is caused by change in neuronal cotransmitter identity
HUI-QUAN LI, WUJI JIANG, LI LING, MARTA PRATELLI, […], AND NICHOLAS C. SPITZER
Science Published:14 Mar 2024
DOI:https://doi.org/10.1126/science.adj5996
Editor’s summary
Traumatic events can lead to anxiety disorders often associated with generalized fear. When this occurs, context-associated fearful behavior generalizes to harmless situations, with adverse consequences on life quality and mental health. Li et al. investigated the mechanisms mediating fear generalization in mice using behavioral, molecular, and electrophysiological approaches (see the Perspective by Hen and Schacher). Fear generalization was found to be caused by a neurotransmitter switch in a subpopulation of serotoninergic neurons of the lateral wings of the dorsal raphe induced by modulation of the glucocorticoid receptor. Blocking this switch prevented fear generalization, suggesting that this mechanism could be targeted for preventing some of the deleterious consequences of acute stress. —Mattia Maroso
Abstract
Overgeneralization of fear to harmless situations is a core feature of anxiety disorders resulting from acute stress, yet the mechanisms by which fear becomes generalized are poorly understood. In this study, we show that generalized fear in mice results from a transmitter switch from glutamate to γ-aminobutyric acid (GABA) in serotonergic neurons of the lateral wings of the dorsal raphe. Similar change in transmitter identity was found in the postmortem brains of individuals with posttraumatic stress disorder (PTSD). Overriding the transmitter switch in mice prevented the acquisition of generalized fear. Corticosterone release and activation of glucocorticoid receptors mediated the switch, and prompt antidepressant treatment blocked the cotransmitter switch and generalized fear. Our results provide important insight into the mechanisms involved in fear generalization.
