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BDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior

Research Article
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Cite this article as: eLife 2018;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.

Data availability

All RNA-seq analysis code and source data are available on the GitHub repository: https://github.com/LieberInstitute/oxt_trap_seq/. Raw sequencing reads are available on SRA under accession code SRP157978.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Kristen R Maynard

    Lieber Institute for Brain Development, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. John W Hobbs

    Lieber Institute for Brain Development, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. BaDoi N Phan

    Lieber Institute for Brain Development, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6331-5980
  4. Amolika Gupta

    Lieber Institute for Brain Development, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sumita Rajpurohit

    Lieber Institute for Brain Development, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Courtney Williams

    Lieber Institute for Brain Development, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Nina Rajpurohit

    Lieber Institute for Brain Development, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Joo Heon Shin

    Lieber Institute for Brain Development, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Andrew E Jaffe

    Lieber Institute for Brain Development, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Keri Martinowich

    Lieber Institute for Brain Development, Baltimore, United States
    For correspondence
    keri.martinowich@libd.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5237-0789

Funding

National Institute of Mental Health (T32MH01533037)

  • Kristen R Maynard

Lieber Institute for Brain Development

  • Keri Martinowich

National Institute of Mental Health (RO1MH105592)

  • Keri Martinowich

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental animal procedures were approved by the Sobran Biosciences Institutional Animal Care and Use Committee (IACUC) under protocol number LIE-004-2015.

Reviewing Editor

  1. Lisa M Monteggia, UT Southwestern Medical Center, United States

Publication history

  1. Received: November 18, 2017
  2. Accepted: September 2, 2018
  3. Accepted Manuscript published: September 7, 2018 (version 1)
  4. Version of Record published: September 12, 2018 (version 2)

Copyright

© 2018, Maynard et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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