PMID- 34058285
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220322
IS  - 1873-2747 (Electronic)
IS  - 0361-9230 (Linking)
VI  - 174
DP  - 2021 Sep
TI  - Forebrain GluN2A overexpression impairs fear extinction and NMDAR-dependent 
      long-term depression in the lateral amygdala.
PG  - 1-10
LID - S0361-9230(21)00162-3 [pii]
LID - 10.1016/j.brainresbull.2021.05.023 [doi]
AB  - N-methyl-d-aspartic acid receptor (NMDAR)-dependent synaptic plasticity at the 
      thalamus-lateral amygdala (T-LA) synapses is related to acquisition and 
      extinction of auditory fear memory. However, the roles of the NMDAR GluN2A 
      subunit in acquisition and extinction of auditory fear memory as well as synaptic 
      plasticity at T-LA synapses remain unclear. Here, using electrophysiologic, 
      molecular biological techniques and behavioral methods, we found that the 
      forebrain specific GluN2A overexpression transgenic (TG) mice exhibited normal 
      acquisition but impaired extinction of auditory fear memory. In addition, in 
      vitro electrophysiological data showed normal basal synaptic transmission and 
      NMDAR-dependent long-term potentiation (LTP) at T-LA synapses, but deficit in 
      NMDAR-dependent long-term depression (LTD) at T-LA synapses in GluN2A TG mice. 
      Consistent with the reduced NMDAR-dependent LTD, 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) 
      internalization was also weakened during NMDAR-dependent LTD in GluN2A TG mice. 
      Taken together, our findings for the first time indicate that GluN2A 
      overexpression impairs extinction of auditory fear memory and NMDAR-dependent LTD 
      at T-LA synapses, which further confirms the close relationship between 
      NMDAR-dependent LTD and fear extinction.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Wang, Jiayue
AU  - Wang J
AD  - Key Laboratory of Brain Functional Genomics, Ministry of Education, School of 
      Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai, 
      200062, China.
FAU - Han, Jiao
AU  - Han J
AD  - Key Laboratory of Brain Functional Genomics, Ministry of Education, School of 
      Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai, 
      200062, China.
FAU - Wang, Shugen
AU  - Wang S
AD  - Key Laboratory of Brain Functional Genomics, Ministry of Education, School of 
      Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai, 
      200062, China.
FAU - Duan, Yanhong
AU  - Duan Y
AD  - Key Laboratory of Brain Functional Genomics, Ministry of Education, School of 
      Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai, 
      200062, China.
FAU - Bao, Chengrong
AU  - Bao C
AD  - Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai, China.
FAU - Luo, Yan
AU  - Luo Y
AD  - Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai, China. Electronic address: ly11087@rjh.com.cn.
FAU - Xue, Qingsheng
AU  - Xue Q
AD  - Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai, China. Electronic address: xqs11260@rjh.com.cn.
FAU - Cao, Xiaohua
AU  - Cao X
AD  - Key Laboratory of Brain Functional Genomics, Ministry of Education, School of 
      Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai, 
      200062, China. Electronic address: xhcao@brain.ecnu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210528
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - VH92ICR8HX (N-methyl D-aspartate receptor subtype 2A)
SB  - IM
MH  - Acoustic Stimulation
MH  - Amygdala/*physiology
MH  - Animals
MH  - Behavior, Animal
MH  - Electrophysiological Phenomena
MH  - Extinction, Psychological/*physiology
MH  - Fear/*psychology
MH  - Gene Expression
MH  - Long-Term Potentiation/genetics/physiology
MH  - Long-Term Synaptic Depression/*genetics/*physiology
MH  - Mice
MH  - Neuronal Plasticity
MH  - Prosencephalon/*metabolism
MH  - Receptors, AMPA/genetics/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/biosynthesis/genetics/*physiology
OTO - NOTNLM
OT  - AMPAR internalization
OT  - Fear extinction
OT  - GluN2A
OT  - LTD
OT  - Thalamus-lateral amygdala synapses
EDAT- 2021/06/01 06:00
MHDA- 2022/03/23 06:00
CRDT- 2021/05/31 20:12
PHST- 2021/03/30 00:00 [received]
PHST- 2021/05/24 00:00 [revised]
PHST- 2021/05/25 00:00 [accepted]
PHST- 2021/06/01 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
PHST- 2021/05/31 20:12 [entrez]
AID - S0361-9230(21)00162-3 [pii]
AID - 10.1016/j.brainresbull.2021.05.023 [doi]
PST - ppublish
SO  - Brain Res Bull. 2021 Sep;174:1-10. doi: 10.1016/j.brainresbull.2021.05.023. Epub 
      2021 May 28.