BDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior

Elife. 2018 Sep 7;7:e33676. doi: 10.7554/eLife.33676.

Abstract

Brain-derived neurotrophic factor (Bdnf) transcription is controlled by several promoters, which drive expression of multiple transcripts encoding an identical protein. We previously reported that BDNF derived from promoters I and II is highly expressed in hypothalamus and is critical for regulating aggression in male mice. Here we report that BDNF loss from these promoters causes reduced sexual receptivity and impaired maternal care in female mice, which is concomitant with decreased oxytocin (Oxt) expression during development. We identify a novel link between BDNF signaling, oxytocin, and maternal behavior by demonstrating that ablation of TrkB selectively in OXT neurons partially recapitulates maternal care impairments observed in BDNF-deficient females. Using translating ribosome affinity purification and RNA-sequencing we define a molecular profile for OXT neurons and delineate how BDNF signaling impacts gene pathways critical for structural and functional plasticity. Our findings highlight BDNF as a modulator of sexually-dimorphic hypothalamic circuits that govern female-typical behaviors.

Keywords: brain-derived neurotrophic factor; hypothalamus; maternal care; mouse; neuroscience; neurotrophins; oxytocin; translating ribosome affinity purification.

Publication types

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

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Estrous Cycle
  • Female
  • Gene Expression Regulation
  • Maternal Behavior
  • Mice, Inbred C57BL
  • Neuronal Plasticity
  • Neurons / metabolism*
  • Oxytocin / genetics
  • Oxytocin / metabolism*
  • Postpartum Period / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, trkB / metabolism*
  • Reproducibility of Results
  • Ribosomes / metabolism
  • Sexual Behavior, Animal
  • Signal Transduction*

Substances

  • Brain-Derived Neurotrophic Factor
  • RNA, Messenger
  • Oxytocin
  • Receptor, trkB