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Exp. Mol. Med., Dec 02 2024, | https://doi.org/10.1038/s12276-024-01365-1 ErbB4 precludes the occurrence of PTSD-like fear responses by supporting the bimodal activity of the central amygdala

Kibong Sung¹, Min-Jae Jeong¹, Taesik Yoo¹, Jung Hoon Jung², Sumin Kang¹, Jong-Yeon Yoo¹, Hyun Jin Kim¹, Kyunghyun Park¹, Jung Hyun Pyo¹, Hyun-Yong Lee¹, Noah Koo¹, Soo-Hee Choi³and Joung-Hun Kim^1,4

¹Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea.
²College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 42601, Republic of Korea.
³Department of Psychiatry, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
⁴Institute of Convergence Science, Yonsei University, Seoul 03722, Republic of Korea

Corresponding author
Correspondence to Joung-Hun Kim.

Abstract

Post-traumatic stress disorder (PTSD) often arises after exposure to traumatic events and is characterized by dysregulated fear responses. Although the associations of erb-b2 receptor tyrosine kinase 4 (ErbB4) with various neuropsychiatric diseases, including schizophrenia and bipolar disorder, have been widely examined, the physiological roles of ErbB4 in PTSD and fear responses remain unclear. Using Cre-dependent ErbB4 knockout (KO) mice, we observed that PTSD-like fear behaviors emerged in ErbB4-deficient mice, particularly in inhibitory neurons. Specifically, the loss of ErbB4 in somatostatin-expressing (SST⁺) neurons was sufficient to induce PTSD-like fear responses. We also adopted the CRISPR/Cas9 system for region-specific KO of ErbB4, which revealed that ErbB4 deletion in SST⁺ neurons of the lateral division of the amygdala (CeL) caused elevated anxiety and PTSD-like fear generalization. Consistent with its physiological role, ErbB4 expression was diminished in CeL^SST neurons from mice that exhibited PTSD-like phenotypes. While fear On and Off cells identified in the CeL displayed distinct responses to conditioned and novel cues, as previously shown, the selectivity of those On and Off cells was compromised in SST^ErbB4-/- and stressed mice, which displayed strong fear generalization. Therefore, the bimodal activity that CeL On/Off cells display is likely required for proper discrimination of fearful stimuli from ambient stimuli, which should be sustained by the presence of ErbB4. Taken together, our data substantiate the correlation between PTSD-like fear responses and ErbB4 expression in CeL^SST neurons and further underscore the functional effects of ErbB4 in CeL^SST neurons, supporting the bimodal responses of CeL neurons.

논문정보

형식Research article
게재일2024년 12월 (BRIC 등록일 2024-12-03)
연구진국내 연구진
분야 생명과학 > 신경생물학

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