A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Academic Article Article uri icon

Overview

MeSH

  • Adolescent
  • Adult
  • Alleles
  • Amygdala
  • Animals
  • Brain Mapping
  • Cues
  • Ethnic Groups
  • Female
  • Gene Knock-In Techniques
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Prefrontal Cortex
  • Young Adult

MeSH Major

  • Brain-Derived Neurotrophic Factor
  • Conditioning, Classical
  • Extinction, Psychological
  • Fear
  • Polymorphism, Single Nucleotide

abstract

  • Mouse models are useful for studying genes involved in behavior, but whether they are relevant to human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat and in the efficacy of treatments that rely on extinction mechanisms, such as exposure therapy.

publication date

  • February 12, 2010

has subject area

  • Adolescent
  • Adult
  • Alleles
  • Amygdala
  • Animals
  • Brain Mapping
  • Brain-Derived Neurotrophic Factor
  • Conditioning, Classical
  • Cues
  • Ethnic Groups
  • Extinction, Psychological
  • Fear
  • Female
  • Gene Knock-In Techniques
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Polymorphism, Single Nucleotide
  • Prefrontal Cortex
  • Young Adult

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2829261

Digital Object Identifier (DOI)

  • 10.1126/science.1181886

PubMed ID

  • 20075215

Additional Document Info

start page

  • 863

end page

  • 866

volume

  • 327

number

  • 5967