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Post-traumatic stress disorder (PTSD) patients have severe fear extinction disorder, but the underlying molecular and neurobiological mechanisms are still unknown. The hippocampus has sub-regional specific functions, however, their involvement in PTSD is unclear. In this study, we used under water trauma (UWT) model rats which exhibit multiple core PTSD symptoms, including anxiety, depression, and impaired fear extinction. In the dorsal or ventral hippocampus, we found that long-term depression at Schaffer collateral and medial perforant pathway was impaired in UWT model rats. Moreover, although the expression levels of ionotropic glutamate receptors including NR2A, NR2B, GluA1, and GluA2 were normal, the activity of alpha calcium/calmodulin-dependent protein kinase II (αCaMKII) significantly increased in both the dorsal and ventral hippocampus of UWT model rats. These findings reveal similar abnormalities in synaptic plasticity and αCaMKII activity in different hippocampal sub-regions of UWT rats. Our results shed light on the region-specific role of the hippocampus in PTSD and provide a theoretical basis for the development of specific treatments for PTSD.


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The neural mechanism of the different sub-regions of hippocampus involved in post-traumatic stress disorder

Show Author's information Zhihong Zuo2,§Xuan Zhou1,§Weihao Zhou1Xiaohua Cao1( )Juzhe Xi3( )Yanhong Duan1( )
Key Laboratory of Brain Functional Genomics, Ministry of Education, School of Life Sciences, East China Normal University, Shanghai 200062, China
Faculty of Education, East China Normal University, Shanghai 200062, China
Shanghai Key Laboratory of Mental Health and Psychological Crisis, Affiliated Mental Health Center (ECNU), Positive Education China Academy, Juzhe Xi’s Master Workroom of Shanghai School Mental Health Service, School of Psychology and Cognitive Science, East China Normal University, Shanghai 200062, China

§ Zhihong Zou and Xuan Zhou contributed equally to this work.

Abstract

Post-traumatic stress disorder (PTSD) patients have severe fear extinction disorder, but the underlying molecular and neurobiological mechanisms are still unknown. The hippocampus has sub-regional specific functions, however, their involvement in PTSD is unclear. In this study, we used under water trauma (UWT) model rats which exhibit multiple core PTSD symptoms, including anxiety, depression, and impaired fear extinction. In the dorsal or ventral hippocampus, we found that long-term depression at Schaffer collateral and medial perforant pathway was impaired in UWT model rats. Moreover, although the expression levels of ionotropic glutamate receptors including NR2A, NR2B, GluA1, and GluA2 were normal, the activity of alpha calcium/calmodulin-dependent protein kinase II (αCaMKII) significantly increased in both the dorsal and ventral hippocampus of UWT model rats. These findings reveal similar abnormalities in synaptic plasticity and αCaMKII activity in different hippocampal sub-regions of UWT rats. Our results shed light on the region-specific role of the hippocampus in PTSD and provide a theoretical basis for the development of specific treatments for PTSD.

Keywords: post-traumatic stress disorder (PTSD), under water trauma (UWT) model rats, long-term depression, alpha calcium/calmodulin-dependent protein kinase II (αCaMKII)

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Publication history

Received: 29 July 2022
Revised: 26 September 2022
Accepted: 21 November 2022
Published: 22 December 2022
Issue date: December 2022

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© The Author(s) 2022

Acknowledgements

This work was supported by grants from National Natural Science Foundation of China (No. 31771177), MOST China-Israel cooperation (No. 2016YFE0130500), Shanghai Science and Technology Commission (No. 20DZ2260300), and National Science and Technology Innovation 2030 Major Program (No. 2022ZD0205100).

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