GABAA presynaptic inhibition regulates the gain and kinetics of retinal output neurons

  1. Jenna Nagy
  2. Briana Ebbinghaus
  3. Mrinalini Hoon
  4. Raunak Sinha  Is a corresponding author
  1. University of Wisconsin, United States

Abstract

Output signals of neural circuits, including the retina, are shaped by a combination of excitatory and inhibitory signals. Inhibitory signals can act presynaptically on axon terminals to control neurotransmitter release and regulate circuit function. However, it has been difficult to study the role of presynaptic inhibition in most neural circuits due to lack of cell-type specific and receptor-type specific perturbations. In this study, we used a transgenic approach to selectively eliminate GABAA inhibitory receptors from select types of second order neurons - bipolar cells - in mouse retina and examined how this affects the light response properties of the well-characterized ON alpha ganglion cell retinal circuit. Selective loss of GABAA receptor-mediated presynaptic inhibition causes an enhanced sensitivity and slower kinetics of light-evoked responses from ON alpha ganglion cells thus highlighting the role of presynaptic inhibition in gain control and temporal filtering of sensory signals in a key neural circuit in the mammalian retina.

Data availability

All source data shown in the figures including some raw data are available in the data repository, Dryad, accessible via this link https://doi.org/10.5061/dryad.bg79cnpb4. Raw datasets are quite large in size and will be made available upon request by the corresponding author.

The following data sets were generated

Article and author information

Author details

  1. Jenna Nagy

    Neuroscience, University of Wisconsin, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Briana Ebbinghaus

    Department of Ophthalmology, University of Wisconsin, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Mrinalini Hoon

    Department of Neuroscience, University of Wisconsin, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Raunak Sinha

    Department of Neuroscience, University of Wisconsin, Madison, United States
    For correspondence
    raunak.sinha@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7553-1274

Funding

National Eye Institute (EY026070)

  • Raunak Sinha

McPherson Eye Research Institute (David and Nancy Walsh Family Professorship in Vision Research)

  • Raunak Sinha

McPherson Eye Research Institute (Rebecca Brown Professorship in Vision Research)

  • Mrinalini Hoon

Research to Prevent Blindness

  • Mrinalini Hoon

National Institute of General Medical Sciences (T32 Graduate Student Fellowship)

  • Jenna Nagy

National Eye Institute (EY031677)

  • Mrinalini Hoon

National Institute of Neurological Disorders and Stroke (T32NS105602)

  • Briana Ebbinghaus

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

Reviewing Editor

  1. Marla B Feller, University of California, Berkeley, United States

Ethics

Animal experimentation: All experiments and animal care were conducted in accordance with the Institutional Animal Care and Use Committee (IACUC) of the University of Wisconsin-Madison and the National Institutes of Health. The protocol was approved by the Animal Care and Use Committee of the University of Wisconsin-Madison (Protocol ID: M006031-R01).

Version history

  1. Received: July 13, 2020
  2. Accepted: April 6, 2021
  3. Accepted Manuscript published: April 27, 2021 (version 1)
  4. Version of Record published: May 10, 2021 (version 2)
  5. Version of Record updated: May 13, 2021 (version 3)

Copyright

© 2021, Nagy 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. Jenna Nagy
  2. Briana Ebbinghaus
  3. Mrinalini Hoon
  4. Raunak Sinha
(2021)
GABAA presynaptic inhibition regulates the gain and kinetics of retinal output neurons
eLife 10:e60994.
https://doi.org/10.7554/eLife.60994

Share this article

https://doi.org/10.7554/eLife.60994

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