Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway

Nat Neurosci. 2014 Jan;17(1):27-9. doi: 10.1038/nn.3591. Epub 2013 Nov 24.

Abstract

Mechanisms controlling release of brain-derived neurotrophic factor (BDNF) in the mesolimbic dopamine reward pathway remain unknown. We report that phasic optogenetic activation of this pathway increases BDNF amounts in the nucleus accumbens (NAc) of socially stressed mice but not of stress-naive mice. This stress gating of BDNF signaling is mediated by corticotrophin-releasing factor (CRF) acting in the NAc. These results unravel a stress context-detecting function of the brain's mesolimbic circuit.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azepines / pharmacology
  • Bacterial Proteins / genetics
  • Benzamides / pharmacology
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Channelrhodopsins
  • Corticotropin-Releasing Hormone / metabolism*
  • Corticotropin-Releasing Hormone / pharmacology
  • Disease Models, Animal
  • Dopamine / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Interpersonal Relations
  • Luminescent Proteins / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microinjections
  • Neurons / metabolism*
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / metabolism*
  • Optogenetics
  • Peptide Fragments / pharmacology
  • Photic Stimulation
  • Statistics, Nonparametric
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology
  • Time Factors
  • Tyrosine 3-Monooxygenase / genetics
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / metabolism*

Substances

  • ANA 12 compound
  • Azepines
  • Bacterial Proteins
  • Benzamides
  • Brain-Derived Neurotrophic Factor
  • Channelrhodopsins
  • Enzyme Inhibitors
  • Luminescent Proteins
  • Peptide Fragments
  • yellow fluorescent protein, Bacteria
  • Corticotropin-Releasing Hormone
  • corticotropin releasing hormone (9-41)
  • Tyrosine 3-Monooxygenase
  • Dopamine