PARIS, an optogenetic method for functionally mapping gap junctions

  1. Ling Wu
  2. Ao Dong
  3. Liting Dong
  4. Shi-Qiang Wang
  5. Yulong Li  Is a corresponding author
  1. Peking University School of Life Sciences, China

Abstract

Cell-cell communication via gap junctions regulates a wide range of physiological processes by enabling the direct intercellular electrical and chemical coupling. However, the in vivo distribution and function of gap junctions remain poorly understood, partly due to the lack of non-invasive tools with both cell-type specificity and high spatiotemporal resolution. Here we developed PARIS (pairing actuators and receivers to optically isolate gap junctions), a new fully genetically encoded tool for measuring the cell-specific gap junctional coupling (GJC). PARIS successfully enabled monitoring of GJC in several cultured cell lines under physiologically relevant conditions and in distinct genetically defined neurons in Drosophila brain, with ~10-sec temporal resolution and sub-cellular spatial resolution. These results demonstrate that PARIS is a robust, highly sensitive tool for mapping functional gap junctions and study their regulation in both health and disease.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Ling Wu

    State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3921-5626
  2. Ao Dong

    State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2821-9528
  3. Liting Dong

    Peking-Tsinghua Center for Life Sciences, Peking University School of Life Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8396-374X
  4. Shi-Qiang Wang

    State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yulong Li

    State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China
    For correspondence
    yulongli@pku.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9166-9919

Funding

National Natural Science Foundation of China (Projects 31371442)

  • Yulong Li

National Natural Science Foundation of China (Projects 31671118)

  • Yulong Li

National Natural Science Foundation of China (Projects 31630035)

  • Shi-Qiang Wang

Ministry of Science and Technology of the People's Republic of China (Grant 2015CB856402)

  • Yulong Li

Ministry of Science and Technology of the People's Republic of China (Grant 2016YFA0500401)

  • Shi-Qiang Wang

Beijing Brain Initiation (Z181100001518004)

  • Yulong Li

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

Copyright

© 2019, Wu 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

  • 7,753
    views
  • 1,265
    downloads
  • 30
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Ling Wu
  2. Ao Dong
  3. Liting Dong
  4. Shi-Qiang Wang
  5. Yulong Li
(2019)
PARIS, an optogenetic method for functionally mapping gap junctions
eLife 8:e43366.
https://doi.org/10.7554/eLife.43366

Share this article

https://doi.org/10.7554/eLife.43366

Further reading

    1. Neuroscience
    Bharath Krishnan, Noah Cowan
    Insight

    Mice can generate a cognitive map of an environment based on self-motion signals when there is a fixed association between their starting point and the location of their goal.

    1. Neuroscience
    Juan Carlos Boffi, Brice Bathellier ... Robert Prevedel
    Research Article

    Sound location coding has been extensively studied at the central nucleus of the mammalian inferior colliculus (CNIC), supporting a population code. However, this population code has not been extensively characterized on the single-trial level with simultaneous recordings or at other anatomical regions like the dorsal cortex of inferior colliculus (DCIC), which is relevant for learning-induced experience dependent plasticity. To address these knowledge gaps, here we made in two complementary ways large-scale recordings of DCIC populations from awake mice in response to sounds delivered from 13 different frontal horizontal locations (azimuths): volumetric two-photon calcium imaging with ~700 cells simultaneously recorded at a relatively low temporal resolution, and high-density single-unit extracellular recordings with ~20 cells simultaneously recorded at a high temporal resolution. Independent of the method, the recorded DCIC population responses revealed substantial trial-to-trial variation (neuronal noise) which was significantly correlated across pairs of neurons (noise correlations) in the passively listening condition. Nevertheless, decoding analysis supported that these noisy response patterns encode sound location on the single-trial basis, reaching errors that match the discrimination ability of mice. The detected noise correlations contributed to minimize the error of the DCIC population code of sound azimuth. Altogether these findings point out that DCIC can encode sound location in a similar format to what has been proposed for CNIC, opening exciting questions about how noise correlations could shape this code in the context of cortico-collicular input and experience-dependent plasticity.