PMID- 29241651
OWN - NLM
STAT- MEDLINE
DCOM- 20181113
LR  - 20191210
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 131
DP  - 2018 Mar 15
TI  - Distinct roles of prelimbic and infralimbic proBDNF in extinction of conditioned 
      fear.
PG  - 11-19
LID - S0028-3908(17)30615-9 [pii]
LID - 10.1016/j.neuropharm.2017.12.018 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) has been investigated for its positive 
      role in regulation of fear acquisition and memory. The precursor of BDNF, 
      proBDNF, has been identified as different protein from its mature form. The 
      prelimbic (PL) and infralimbic (IL) sub-regions of the medial prefrontal cortex 
      (mPFC) are functionally distinct in fear behavior. However, the role of PL and IL 
      proBDNF in fear memory is unclear. Here, through the infusion of 
      cleavage-resistant proBDNF and its antibody, we identified the dissociable roles 
      of PL and IL proBDNF in fear expression and extinction memory as well as explored 
      proBDNF's potential mechanism of action. The results suggest that the infusion of 
      proBDNF in the IL facilitates induction of fear extinction, while infusion in the 
      PL depresses fear expression. Blocking proBDNF by using its antibody disrupted 
      the acquisition of fear extinction in the IL, but not the PL. Furthermore, 
      proBDNF-induced extinction was sufficient for extinguishing new and older 
      memories, and required NR2B, but not NR2A, -containing NMDA receptors. We also 
      observed extinction-related proBDNF expression increased in the PL and IL during 
      successful fear expression and extinction, respectively. Importantly, enhanced 
      proBDNF was required for maintaining an extinguished behavior. The extinction 
      effects of proBDNF did not involve degrading the original fear memory. Therefore, 
      proBDNF in the IL and PL differentially contribute to the inhibitory control of 
      fear extinction behavior. Our findings provide a strong link between proBDNF 
      activity and deficits in fear extinction, a hallmark of several psychiatric 
      disorders.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Sun, Wei
AU  - Sun W
AD  - Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou 
      University of Chinese Medicine, 510006 Guangzhou, China.
FAU - Li, Xiaoliang
AU  - Li X
AD  - Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou 
      University of Chinese Medicine, 510006 Guangzhou, China.
FAU - An, Lei
AU  - An L
AD  - Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou 
      University of Chinese Medicine, 510006 Guangzhou, China; Department of 
      Physiology, University of Saskatchewan, S7N 5E5 Saskatoon, Canada. Electronic 
      address: al_totti@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171211
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 
      (5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione)
RN  - 0 (Antibodies)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Phenols)
RN  - 0 (Piperidines)
RN  - 0 (Quinoxalines)
RN  - 0 (Ro 25-6981)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Brain-Derived Neurotrophic Factor/immunology/*metabolism
MH  - Conditioning, Psychological/drug effects/*physiology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Extinction, Psychological/drug effects/*physiology
MH  - Fear/drug effects/*physiology
MH  - Male
MH  - Phenols/pharmacology
MH  - Piperidines/pharmacology
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Quinoxalines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - Fear extinction
OT  - NMDA receptors
OT  - mPFC
OT  - proBDNF
EDAT- 2017/12/16 06:00
MHDA- 2018/11/14 06:00
CRDT- 2017/12/16 06:00
PHST- 2017/07/04 00:00 [received]
PHST- 2017/11/10 00:00 [revised]
PHST- 2017/12/09 00:00 [accepted]
PHST- 2017/12/16 06:00 [pubmed]
PHST- 2018/11/14 06:00 [medline]
PHST- 2017/12/16 06:00 [entrez]
AID - S0028-3908(17)30615-9 [pii]
AID - 10.1016/j.neuropharm.2017.12.018 [doi]
PST - ppublish
SO  - Neuropharmacology. 2018 Mar 15;131:11-19. doi: 10.1016/j.neuropharm.2017.12.018. 
      Epub 2017 Dec 11.