Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells.

Autor:	Li M; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Yang XK; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Yang J; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Li TX; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Cui C; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Peng X; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Lei J; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Ren K; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China., Ming J; Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, Hubei 430022, P.R. China., Zhang P; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China; Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China; Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei 430030, P.R. China. Electronic address: zhangpei@hust.edu.cn., Tian B; Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China; School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei 430081, P.R. China; Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China; Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei 430030, P.R. China. Electronic address: tianbo@mails.tjmu.edu.cn.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2024 Sep 25; Vol. 112 (18), pp. 3192-3210.e6. Date of Electronic Publication: 2024 Jul 19.
DOI:	10.1016/j.neuron.2024.06.026
Abstrakt:	Erasing traumatic memory during memory reconsolidation is a promising retrieval-extinction strategy for post-traumatic stress disorder (PTSD). Here, we developed an acute social defeat stress (SDS) mouse model with short-term and re-exposure-evoked long-term social avoidance. SDS-associated traumatic memories were identified to be stored in basolateral amygdala (BLA) engram cells. A single intraperitoneal administration of subanesthetic-dose ketamine within, but not beyond, the re-exposure time window significantly alleviates SDS-induced social avoidance, which reduces the activity and quantity of reactivated BLA engram cells. Furthermore, activation or inhibition of dopaminergic projections from the ventral tegmental area to the BLA effectively mimics or blocks the therapeutic effect of re-exposure with ketamine and is dopamine D2 receptor dependent. Single-cell RNA sequencing reveals that re-exposure with ketamine triggered significant changes in memory-related pathways in the BLA. Together, our research advances the understanding of how ketamine mitigates PTSD symptoms and offers promising avenues for developing more effective treatments for trauma-related disorders. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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