1. Neuroscience
Download icon

Ca2+ sensor synaptotagmin-1 mediates exocytosis in mammalian photoreceptors

Research Article
  • Cited 7
  • Views 1,597
  • Annotations
Cite this article as: eLife 2019;8:e45946 doi: 10.7554/eLife.45946

Abstract

To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca2+ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous release frequency was unchanged in cones but increased in rods lacking Syt1. Loss of Syt1 did not alter synaptic anatomy or reduce Ca2+ currents. These results suggest that Syt1 mediates both phasic and tonic release at photoreceptor synapses, revealing unexpected flexibility in the ability of Syt1 to regulate Ca2+-dependent synaptic transmission.

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 Figure 9.

Article and author information

Author details

  1. Justin J Grassmeyer

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9624-9027
  2. Asia L Cahill

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Cassandra L Hays

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Cody Barta

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rolen M Quadros

    Mouse Genome Engineering Core Facility, Vice Chancellor for Research Office, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9798-9622
  6. Channabasavaiah B Gurumurthy

    Mouse Genome Engineering Core Facility, Vice Chancellor for Research Office, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8022-4033
  7. Wallace B Thoreson

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    For correspondence
    wbthores@unmc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7104-042X

Funding

National Eye Institute (EY10542)

  • Wallace B Thoreson

Research to Prevent Blindness (Senior Scientific Investigator)

  • Wallace B Thoreson

National Eye Institute (EY28848)

  • Justin J Grassmeyer

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

Ethics

Animal experimentation: All animal care and handling protocols were approved by the University of Nebraska Medical Center Institutional Animal Care and Use Committee (protocols 15-027-00 and 15-028-04).

Reviewing Editor

  1. Reinhard Jahn, Max Planck Institute for Biophysical Chemistry, Germany

Publication history

  1. Received: February 9, 2019
  2. Accepted: June 6, 2019
  3. Accepted Manuscript published: June 7, 2019 (version 1)
  4. Version of Record published: June 21, 2019 (version 2)

Copyright

© 2019, Grassmeyer 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

  • 1,597
    Page views
  • 246
    Downloads
  • 7
    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
    Romy Frömer et al.
    Research Article Updated

    Influential theories emphasize the importance of predictions in learning: we learn from feedback to the extent that it is surprising, and thus conveys new information. Here, we explore the hypothesis that surprise depends not only on comparing current events to past experience, but also on online evaluation of performance via internal monitoring. Specifically, we propose that people leverage insights from response-based performance monitoring – outcome predictions and confidence – to control learning from feedback. In line with predictions from a Bayesian inference model, we find that people who are better at calibrating their confidence to the precision of their outcome predictions learn more quickly. Further in line with our proposal, EEG signatures of feedback processing are sensitive to the accuracy of, and confidence in, post-response outcome predictions. Taken together, our results suggest that online predictions and confidence serve to calibrate neural error signals to improve the efficiency of learning.

    1. Neuroscience
    Jonas Hansen Kymre et al.
    Research Article

    The pheromone system of heliothine moths is an optimal model for studying principles underlying higher-order olfactory processing. In Helicoverpa armigera, three male-specific glomeruli receive input about three female-produced signals, the primary pheromone component, serving as an attractant, and two minor constituents, serving a dual function, i.e. attraction versus inhibition of attraction. From the antennal-lobe glomeruli, the information is conveyed to higher olfactory centers, including the lateral protocerebrum, via three main paths – of which the medial tract is the most prominent. In this study, we traced physiologically identified medial-tract projection neurons from each of the three male‑specific glomeruli with the aim of mapping their terminal branches in the lateral protocerebrum. Our data suggest that the neurons’ wide-spread projections are organized according to behavioral significance, including a spatial separation of signals representing attraction versus inhibition – however, with a unique capacity of switching behavioral consequence based on the amount of the minor components.