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

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)
  4. Version of Record published: April 16, 2021 (version 2)

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.

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  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
  16. Xia-Jing Tong
(2021)
Male pheromones modulate synaptic transmission at the C. elegans neuromuscular junction in a sexually dimorphic manner
eLife 10:e67170.
https://doi.org/10.7554/eLife.67170

Further reading

    1. Developmental Biology
    2. Neuroscience
    Emily L Heckman, Chris Q Doe
    Research Advance

    The organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously we developed a model system in the Drosophila ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly respond to developmental variability in presynaptic location and input strength.

    1. Epidemiology and Global Health
    2. Neuroscience
    Lorenza Dall'Aglio, Hannah H Kim ... Henning Tiemeier
    Research Article Updated

    Background:

    Associations between attention-deficit/hyperactivity disorder (ADHD) and brain morphology have been reported, although with several inconsistencies. These may partly stem from confounding bias, which could distort associations and limit generalizability. We examined how associations between brain morphology and ADHD symptoms change with adjustments for potential confounders typically overlooked in the literature (aim 1), and for the intelligence quotient (IQ) and head motion, which are generally corrected for but play ambiguous roles (aim 2).

    Methods:

    Participants were 10-year-old children from the Adolescent Brain Cognitive Development (N = 7722) and Generation R (N = 2531) Studies. Cortical area, volume, and thickness were measured with MRI and ADHD symptoms with the Child Behavior Checklist. Surface-based cross-sectional analyses were run.

    Results:

    ADHD symptoms related to widespread cortical regions when solely adjusting for demographic factors. Additional adjustments for socioeconomic and maternal behavioral confounders (aim 1) generally attenuated associations, as cluster sizes halved and effect sizes substantially reduced. Cluster sizes further changed when including IQ and head motion (aim 2), however, we argue that adjustments might have introduced bias.

    Conclusions:

    Careful confounder selection and control can help identify more robust and specific regions of associations for ADHD symptoms, across two cohorts. We provided guidance to minimizing confounding bias in psychiatric neuroimaging.

    Funding:

    Authors are supported by an NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200 to HT) for HT, LDA, SL, and the Sophia Foundation S18-20, and Erasmus University and Erasmus MC Fellowship for RLM.