恐怖は脳の中でどのように展開するのか(How Fear Unfolds inside Our Brains)

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2024-03-14 カリフォルニア大学サンディエゴ校(UCSD)

恐怖は脳の中でどのように展開するのか(How Fear Unfolds inside Our Brains)
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

研究によれば、ストレスの影響で脳内の神経伝達物質が切り替わり、一般化された恐怖反応が引き起こされることが明らかになりました。この研究は、UCサンディエゴの神経生物学者が行い、『Science』誌に掲載されました。さらに、アデノ随伴ウイルスを用いた遺伝子抑制や抗うつ薬の投与が恐怖反応を防ぐことが示されました。これにより、恐怖反応を引き起こす神経回路を特定し、対処法を見出す可能性が高まりました。

<関連情報>

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.

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