1. Neuroscience
Download icon

Male pheromones modulate synaptic transmission at the C. elegans neuromuscular junction in a sexually dimorphic manner

  1. Kang-Ying Qian
  2. Wan-Xin Zeng
  3. Yue Hao
  4. Xian-Ting Zeng
  5. Haowen Liu
  6. Lei Li
  7. Lili Chen
  8. Fu-min Tian
  9. Cindy Chang
  10. Qi Hall
  11. Chun-Xue Song
  12. Shangbang Gao
  13. Zhi-Tao Hu
  14. Josh M Kaplan
  15. Qian Li  Is a corresponding author
  16. Xia-Jing Tong  Is a corresponding author
  1. ShanghaiTech University, China
  2. The University of Queensland, Australia
  3. College of Life Science and Technology, China
  4. Massachusetts General Hospital, United States
  5. Shanghai Jiao Tong University School of Medicine, China
Research Article
  • Cited 0
  • Views 275
  • Annotations
Cite this article as: eLife 2021;10:e67170 doi: 10.7554/eLife.67170

Abstract

The development of functional synapses in the nervous system is important for animal physiology and behaviors, and its disturbance has been linked with many neurodevelopmental disorders. The synaptic transmission efficacy can be modulated by the environment to accommodate external changes, which is crucial for animal reproduction and survival. However, the underlying plasticity of synaptic transmission remains poorly understood. Here we show that in C. elegans, the male environment increases the hermaphrodite cholinergic transmission at the neuromuscular junction (NMJ), which alters hermaphrodites' locomotion velocity and mating efficiency. We identify that the male-specific pheromones mediate this synaptic transmission modulation effect in a developmental stage-dependent manner. Dissection of the sensory circuits reveals that the AWB chemosensory neurons sense those male pheromones and further transduce the information to NMJ using cGMP signaling. Exposure of hermaphrodites to the male pheromones specifically increases the accumulation of presynaptic CaV2 calcium channels and clustering of postsynaptic acetylcholine receptors at cholinergic synapses of NMJ, which potentiates cholinergic synaptic transmission. Thus, our study demonstrates a circuit mechanism for synaptic modulation and behavioral flexibility by sexual dimorphic pheromones.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided. For other information (such as primers), we already included them in the methods.

Article and author information

Author details

  1. Kang-Ying Qian

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Wan-Xin Zeng

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yue Hao

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Xian-Ting Zeng

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Haowen Liu

    Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Lei Li

    Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Lili Chen

    Huazhong University of Science and Tehcnology, College of Life Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Fu-min Tian

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Cindy Chang

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Qi Hall

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Chun-Xue Song

    Center for Brain Science, Shanghai Children's Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Shangbang Gao

    Huazhong University of Science and Tehcnology, College of Life Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5431-4628
  13. Zhi-Tao Hu

    Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2948-3339
  14. Josh M Kaplan

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7418-7179
  15. Qian Li

    Center for Brain Science, Shanghai Children's Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    For correspondence
    liqian@shsmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1300-3377
  16. Xia-Jing Tong

    School of Life Science and Technology, ShanghaiTech University, Shanghai, China
    For correspondence
    tongxj@shanghaitech.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5634-1136

Funding

Basic Research Project from the Science and Technology Commission (19JC1414100)

  • Xia-Jing Tong

Shanghai Pujiang Program (18PJ1407600)

  • Xia-Jing Tong

Shanghai Pujiang Program (17PJ1405400)

  • Qian Li

Shanghai Brain-Intelligence Project from the Science and Technology Commission of Shanghai Municipality (18JC1420302)

  • Qian Li

Program for Special Appointment at Shanghai Institutions of Higher Learning (QD2018017)

  • Qian Li

Innovative research team of high-level local universities in Shanghai, National Institute of Neurological Disorder and Stroke (NS32196)

  • Josh M Kaplan

National Institutes of Health research grant (NEI 1R21EY029450-01)

  • Josh M Kaplan

National Health and Medical Research Council (APP1122351)

  • Zhi-Tao Hu

National Natural Science Foundation of China (31741054)

  • Xia-Jing Tong

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

Reviewing Editor

  1. Douglas Portman, University of Rochester, United States

Publication history

  1. Received: February 2, 2021
  2. Accepted: March 30, 2021
  3. Accepted Manuscript published: March 31, 2021 (version 1)

Copyright

© 2021, Qian 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.

Metrics

  • 275
    Page views
  • 69
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Stanley Heinze
    Insight

    Fruit flies rely on an intricate neural pathway to process polarized light signals in order to inform their internal compass about the position of the Sun.

    1. Neuroscience
    Zachariah Bertels et al.
    Research Article

    Migraine is the third most prevalent disease worldwide but the mechanisms that underlie migraine chronicity are poorly understood. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on dynamic microtubules. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, α-tubulin. We use validated mouse models of migraine to show that HDAC6-inhibition is a promising migraine treatment and reveal an undiscovered cytoarchitectural basis for migraine chronicity. The human migraine trigger, nitroglycerin, produced chronic migraine-associated pain and decreased neurite growth in headache-processing regions, which were reversed by HDAC6 inhibition. Cortical spreading depression (CSD), a physiological correlate of migraine aura, also decreased cortical neurite growth, while HDAC6-inhibitor restored neuronal complexity and decreased CSD. Importantly, a calcitonin gene-related peptide receptor antagonist also restored blunted neuronal complexity induced by nitroglycerin. Our results demonstrate that disruptions in neuronal cytoarchitecture are a feature of chronic migraine, and effective migraine therapies might include agents that restore microtubule/neuronal plasticity.