PMID- 25127683
OWN - NLM
STAT- MEDLINE
DCOM- 20150526
LR  - 20211021
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Print)
IS  - 0166-4328 (Linking)
VI  - 274
DP  - 2014 Nov 1
TI  - Mice lacking TrkB in parvalbumin-positive cells exhibit sexually dimorphic 
      behavioral phenotypes.
PG  - 219-25
LID - S0166-4328(14)00523-3 [pii]
LID - 10.1016/j.bbr.2014.08.011 [doi]
AB  - Activity-dependent brain-derived neurotrophic factor (BDNF) signaling through 
      receptor tyrosine kinase B (TrkB) is required for cued fear memory consolidation 
      and extinction. Although BDNF is primarily secreted from glutamatergic neurons, 
      TrkB is expressed by other genetically defined cells whose contributions to the 
      behavioral effects of BDNF remain poorly understood. Parvalbumin (PV)-positive 
      interneurons, which are highly enriched in TrkB, are emerging as key regulators 
      of fear memory expression. We therefore hypothesized that activity-dependent BDNF 
      signaling in PV-interneurons may modulate emotional learning. To test this 
      hypothesis, we utilized the LoxP/Cre system for conditional deletion of TrkB in 
      PV-positive cells to examine the impact of cell-autonomous BDNF signaling on 
      Pavlovian fear conditioning and extinction. However, behavioral abnormalities 
      indicative of vestibular dysfunction precluded the use of homozygous conditional 
      knockouts in tests of higher cognitive functioning. While vestibular dysfunction 
      was apparent in both sexes, female conditional knockouts exhibited an exacerbated 
      phenotype, including extreme motor hyperactivity and circling behavior, compared 
      to their male littermates. Heterozygous conditional knockouts were spared of 
      vestibular dysfunction. While fear memory consolidation was unaffected in 
      heterozygotes of both sexes, males exhibited impaired extinction consolidation 
      compared to their littermate controls. Our findings complement evidence from 
      human and rodent studies suggesting that BDNF signaling promotes consolidation of 
      extinction and point to PV-positive neurons as a discrete population that 
      mediates these effects in a sex-specific manner.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Lucas, Elizabeth K
AU  - Lucas EK
AD  - Fishberg Department of Neuroscience and the Friedman Brain Institute, Icahn 
      School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1065, New York, NY 
      10029, USA.
FAU - Jegarl, Anita
AU  - Jegarl A
AD  - Fishberg Department of Neuroscience and the Friedman Brain Institute, Icahn 
      School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1065, New York, NY 
      10029, USA.
FAU - Clem, Roger L
AU  - Clem RL
AD  - Fishberg Department of Neuroscience and the Friedman Brain Institute, Icahn 
      School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1065, New York, NY 
      10029, USA. Electronic address: roger.clem@mssm.edu.
LA  - eng
GR  - R01 MH105414/MH/NIMH NIH HHS/United States
GR  - T32 MH096678/MH/NIMH NIH HHS/United States
GR  - MH096678/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140812
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Bacterial Proteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Parvalbumins)
RN  - 0 (yellow fluorescent protein, Bacteria)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/genetics/metabolism
MH  - Behavior, Animal/*physiology
MH  - Brain/cytology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Exploratory Behavior/physiology
MH  - Extinction, Psychological/physiology
MH  - Female
MH  - Interneurons/*metabolism
MH  - Learning Disabilities/genetics
MH  - Luminescent Proteins/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Parvalbumins/genetics/*metabolism
MH  - *Phenotype
MH  - Receptor, trkB/*deficiency/genetics
MH  - *Sex Characteristics
MH  - Signal Transduction/genetics
MH  - Stereotypic Movement Disorder/genetics
MH  - Vestibular Diseases/genetics
PMC - PMC5063750
MID - NIHMS626633
OTO - NOTNLM
OT  - Circling
OT  - Extinction
OT  - Fear conditioning
OT  - Ntrk2
OT  - Vestibular
EDAT- 2014/08/17 06:00
MHDA- 2015/05/27 06:00
PMCR- 2016/10/13
CRDT- 2014/08/17 06:00
PHST- 2014/03/20 00:00 [received]
PHST- 2014/07/09 00:00 [revised]
PHST- 2014/08/04 00:00 [accepted]
PHST- 2014/08/17 06:00 [entrez]
PHST- 2014/08/17 06:00 [pubmed]
PHST- 2015/05/27 06:00 [medline]
PHST- 2016/10/13 00:00 [pmc-release]
AID - S0166-4328(14)00523-3 [pii]
AID - 10.1016/j.bbr.2014.08.011 [doi]
PST - ppublish
SO  - Behav Brain Res. 2014 Nov 1;274:219-25. doi: 10.1016/j.bbr.2014.08.011. Epub 2014 
      Aug 12.