Gjd2b-mediated gap junctions promote glutamatergic synapse formation and dendritic elaboration in Purkinje neurons

Abstract

Gap junctions between neurons serve as electrical synapses, in addition to conducting metabolites and signaling molecules. During development, early-appearing gap junctions are thought to prefigure chemical synapses, which appear much later. We present evidence for this idea at a central, glutamatergic synapse and provide some mechanistic insights. Loss or reduction in the levels of the gap junction protein Gjd2b decreased the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in cerebellar Purkinje neurons (PNs) in larval zebrafish. Ultrastructural analysis in the molecular layer showed decreased synapse density. Further, mEPSCs had faster kinetics and larger amplitudes in mutant PNs, consistent with their stunted dendritic arbors. Time-lapse microscopy in wild type and mutant PNs reveals that Gjd2b puncta promote the elongation of branches and that CaMKII may be a critical mediator of this process. These results demonstrate that Gjd2b-mediated gap junctions regulate glutamatergic synapse formation and dendritic elaboration in PNs.

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. Sahana Sitaraman

    Neurobiology, National Centre for Biological Sciences, Bangalore, India
    Competing interests
    No competing interests declared.
  2. Gnaneshwar Yadav

    Neurobiology, National Centre for Biological Sciences, Bangalore, India
    Competing interests
    No competing interests declared.
  3. Vandana Agarwal

    Neurobiology, National Centre for Biological Sciences, Bangalore, India
    Competing interests
    No competing interests declared.
  4. Shaista Jabeen

    Neurobiology, National Centre for Biological Sciences, Bangalore, India
    Competing interests
    No competing interests declared.
  5. Shivangi Verma

    Neurobiology, National Centre for Biological Sciences, Bangalore, India
    Competing interests
    No competing interests declared.
  6. Meha Jadhav

    Neurobiology, National Centre for Biological Sciences, Bangalore, India
    Competing interests
    No competing interests declared.
  7. Vatsala Thirumalai

    Neurobiology, National Centre for Biological Sciences, Bangalore, India
    For correspondence
    vatsala@ncbs.res.in
    Competing interests
    Vatsala Thirumalai, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2318-5023

Funding

The Wellcome Trust DBT India Alliance (500040/Z/09/Z and IA/S/17/2/503297)

  • Vatsala Thirumalai

Department of Biotechnology, Ministry of Science and Technology, India (BT/PR4983/MED/30/790/2012)

  • Vatsala Thirumalai

Science and Engineering Research Board (EMR/2015/000595)

  • Vatsala Thirumalai

Department of Atomic Energy, Government of India (12-R&DTFR-5.04-0800)

  • Vatsala Thirumalai

Council of Scientific and Industrial Research, India

  • Shaista Jabeen

Science and Engineering Research Board (YSS/2015/000908)

  • Gnaneshwar Yadav

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

Ethics

Animal experimentation: Institutional Animal Ethics and Biosafety committee approvals were obtained for all procedures adopted in this study ( NCB/IAEC/VT-1/2011 and TFR/NCBS/14-IBSC/VT-1/2011). Larvae and adults were reared using standard procedures (Westerfield, 2000).

Reviewing Editor

  1. Hollis T Cline, The Scripps Research Institute, United States

Publication history

  1. Preprint posted: January 31, 2020 (view preprint)
  2. Received: March 7, 2021
  3. Accepted: August 3, 2021
  4. Accepted Manuscript published: August 4, 2021 (version 1)
  5. Version of Record published: August 23, 2021 (version 2)

Copyright

© 2021, Sitaraman 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. Sahana Sitaraman
  2. Gnaneshwar Yadav
  3. Vandana Agarwal
  4. Shaista Jabeen
  5. Shivangi Verma
  6. Meha Jadhav
  7. Vatsala Thirumalai
(2021)
Gjd2b-mediated gap junctions promote glutamatergic synapse formation and dendritic elaboration in Purkinje neurons
eLife 10:e68124.
https://doi.org/10.7554/eLife.68124

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