The components of an electrical synapse as revealed by expansion microscopy of a single synaptic contact

  1. Sandra P Cárdenas-García
  2. Sundas Ijaz
  3. Alberto E Pereda  Is a corresponding author
  1. Albert Einstein College of Medicine, United States

Abstract

Most nervous systems combine both transmitter-mediated and direct cell-cell communication, known as 'chemical' and 'electrical' synapses, respectively. Chemical synapses can be identified by their multiple structural components. Electrical synapses are, on the other hand, generally defined by the presence of a 'gap junction' (a cluster of intercellular channels) between two neuronal processes. However, while gap junctions provide the communicating mechanism, it is unknown whether electrical transmission requires the contribution of additional cellular structures. We investigated this question at identifiable single synaptic contacts on the zebrafish Mauthner cells, at which gap junctions coexist with specializations for neurotransmitter release and where the contact unequivocally defines the anatomical limits of a synapse. Expansion microscopy of these single contacts revealed a detailed map of the incidence and spatial distribution of proteins pertaining to various synaptic structures. Multiple gap junctions of variable size were identified by the presence of their molecular components. Remarkably, most of the synaptic contact's surface was occupied by interleaving gap junctions and components of adherens junctions, suggesting a close functional association between these two structures. In contrast, glutamate receptors were confined to small peripheral portions of the contact, indicating that most of the synaptic area functions as an electrical synapse. Thus, our results revealed the overarching organization of an electrical synapse that operates with not one, but multiple gap junctions, in close association with structural and signaling molecules known to be components of adherens junctions. The relationship between these intercellular structures will aid in establishing the boundaries of electrical synapses found throughout animal connectomes and provide insight into the structural organization and functional diversity of electrical synapses.

Data availability

All data generated and analyzed for Figures 2D-F; 3E-F; 4C-F; 5D-E; 6B,D, F; 7A-D; and Supp Figure 1B are available as source data Excel files on G-Node (https://gin.g-node.org/apereda/Cardenas); DOI: 10.12751/g-node.3d7s8d.

The following data sets were generated

Article and author information

Author details

  1. Sandra P Cárdenas-García

    Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sundas Ijaz

    Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0009-0005-8199-7598
  3. Alberto E Pereda

    Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, United States
    For correspondence
    alberto.pereda@einsteinmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8283-8768

Funding

National Institute on Deafness and Other Communication Disorders (R01DC011099)

  • Alberto E Pereda

National Institute of Neurological Disorders and Stroke (R21NS085772)

  • Alberto E Pereda

National Institute of Mental Health (RF1MH120016)

  • Alberto E Pereda

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#00001029) of the Albert Einstein College of Medicine.

Copyright

© 2024, Cárdenas-García 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. Sandra P Cárdenas-García
  2. Sundas Ijaz
  3. Alberto E Pereda
(2024)
The components of an electrical synapse as revealed by expansion microscopy of a single synaptic contact
eLife 13:e91931.
https://doi.org/10.7554/eLife.91931

Share this article

https://doi.org/10.7554/eLife.91931

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