Qianqian Cao1, Yuan Wei2, Jialin Deng1, Junfeng Li1, Yanhua Huang1, Yuke Li1, Ji-Chun Zhang1, Zili Zhang3, Song Lin4. 1. Department of Physiology, School of Medicine, Jinan University, Guangzhou, 510632, China. 2. Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sports University, Guangzhou, 510500, China. 3. Department of Reproductive Medicine Center, The First People's Hospital of Foshan (Affiliated FoShan Hospital of Sun Yat-Sen University), Foshan, China. zhangzili11@hotmail.com. 4. Department of Physiology, School of Medicine, Jinan University, Guangzhou, 510632, China. linsong@jnu.edu.cn.
Abstract
RATIONALE: Forgetting of fear memory is a current medical therapy for posttraumatic stress disorder (PTSD), and hippocampal long-term depression (LTD) may be the underlying mechanism. Neuregulin 1 (NRG1), a trophic factor, reportedly modulates memory consolidation and synaptic plasticity. METHODS: Fear memory was assessed using contextual fear conditioning. Electrophysiology was used to measure LTD and GABAergic transmission in the hippocampus. OBJECTIVES: To determine the contribution of hippocampal NRG1 to fear memory forgetting and low-frequency stimulation (LFS)-induced LTD. RESULTS: Administration of NRG1 in the hippocampus accelerated forgetting of contextual fear memories. Furthermore, NRG1 had no effect on low-frequency stimulation-induced LTD in young mice but significantly facilitated the induction of LTD and GABAergic transmission in adult animals. More importantly, NRG1-facilitated LTD induction in adult mice could be blocked by inhibition of GABAA receptors and NMDAR activation. CONCLUSION: These findings suggest a role for NRG1 in fear memory forgetting and hippocampal LTD, providing a potential target for the development of drug-assisted PTSD therapy.
RATIONALE: Forgetting of fear memory is a current medical therapy for posttraumatic stress disorder (PTSD), and hippocampal long-term depression (LTD) may be the underlying mechanism. Neuregulin 1 (NRG1), a trophic factor, reportedly modulates memory consolidation and synaptic plasticity. METHODS: Fear memory was assessed using contextual fear conditioning. Electrophysiology was used to measure LTD and GABAergic transmission in the hippocampus. OBJECTIVES: To determine the contribution of hippocampal NRG1 to fear memory forgetting and low-frequency stimulation (LFS)-induced LTD. RESULTS: Administration of NRG1 in the hippocampus accelerated forgetting of contextual fear memories. Furthermore, NRG1 had no effect on low-frequency stimulation-induced LTD in young mice but significantly facilitated the induction of LTD and GABAergic transmission in adult animals. More importantly, NRG1-facilitated LTD induction in adult mice could be blocked by inhibition of GABAA receptors and NMDAR activation. CONCLUSION: These findings suggest a role for NRG1 in fear memory forgetting and hippocampal LTD, providing a potential target for the development of drug-assisted PTSD therapy.
Entities:
Keywords:
Adult mice; Fear memory forgetting; GABAergic transmission; Hippocampus; LTD; PTSD; Young mice