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

Abstract
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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 GABA_A 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 GABA_A 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

(2021) GABAA presynaptic inhibition regulates the gain and kinetics of retinal output neurons
Dryad Digital Repository, doi: 10.5061/dryad.bg79cnpb4.

https://doi.org/10.5061/dryad.bg79cnpb4

Article and author information

Author details

Jenna Nagy

Neuroscience, University of Wisconsin, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Briana Ebbinghaus

Department of Ophthalmology, University of Wisconsin, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Mrinalini Hoon

Department of Neuroscience, University of Wisconsin, Madison, United States

Competing interests
The authors declare that no competing interests exist.
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.

"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.

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).

Copyright

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.