ArticlePLoS biology2019
Novel hybrid action of GABA mediates inhibitory feedback in the mammalian retina.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Role of the C-terminal domain in modifying pH-dependent regulation of CaChannels (Austin, Tex.) · 2025Article
- The sodium-bicarbonate cotransporter Slc4a5 mediates feedback at the first synapse of vision.Neuron · 2024Article
- Presynaptic Proteins and Their Roles in Visual Processing by the Retina.Annual review of vision science · 2024Review
- The role of syntaxins in retinal function and health.Frontiers in cellular neuroscience · 2024Review
- Clarifying the composition of the ATP consumption factors required for maintaining ion homeostasis in mouse rod photoreceptors.Scientific reports · 2023Article
- The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases.Biomedicines · 2023Review
- Origin of Retinal Oscillatory Potentials in the Mouse, a Tool to Specifically Locate Retinal Damage.International journal of molecular sciences · 2023Article
- Dye coupling of horizontal cells in the primate retina.Frontiers in ophthalmology · 2023Article
- Classical center-surround receptive fields facilitate novel object detection in retinal bipolar cells.Nature communications · 2022Article
- Calcium Channels in Retinal Function and Disease.Annual review of vision science · 2022Review
- Multiple Invagination Patterns and Synaptic Efficacy in Primate and Mouse Rod Synaptic Terminals.Investigative ophthalmology & visual science · 2022Article
- Visual processing: When two synaptic strata are better than one.Current biology : CB · 2022Article
- Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling.Current biology : CB · 2022Article
- Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A multiscale continuum model of the vertebrate outer retina: The temporal dynamics of background-induced flicker enhancement.Journal of theoretical biology · 2021Article
- Antagonistic surround responses in different cones are mediated by feedback synapses from different horizontal cells.Vision research · 2021Article
- Synaptic Scaffolds, Ion Channels and Polyamines in Mouse Photoreceptor Synapses: Anatomy of a Signaling Complex.Frontiers in cellular neuroscience · 2021Article
- NKCC1, an Elusive Molecular Target in Brain Development: Making Sense of the Existing Data.Cells · 2020Review
- Glycinergic and GABAergic interneurons shift the location and differentially alter the size of ganglion cell receptive field centers in the mammalian retina.Vision research · 2020Article
- Degenerated Cones in Cultured Human Retinas Can Successfully Be Optogenetically Reactivated.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The stream of visual information sent from photoreceptors to second-order bipolar cells is intercepted by laterally interacting horizontal cells that generate feedback to optimize and improve the efficiency of signal transmission. The mechanisms underlying the regulation of graded photoreceptor synaptic output in this nonspiking network have remained elusive. Here, we analyze with patch clamp recording the novel mechanisms by which horizontal cells control pH in the synaptic cleft to modulate photoreceptor neurotransmitter release. First, we show that mammalian horizontal cells respond to their own GABA release and that the results of this autaptic action affect cone voltage-gated Ca2+ channel (CaV channel) gating through changes in pH. As a proof-of-principle, we demonstrate that chemogenetic manipulation of horizontal cells with exogenous anion channel expression mimics GABA-mediated cone CaV channel inhibition. Activation of these GABA receptor anion channels can depolarize horizontal cells and increase cleft acidity via Na+/H+ exchanger (NHE) proton extrusion, which results in inhibition of cone CaV channels. This action is effectively counteracted when horizontal cells are sufficiently hyperpolarized by increased GABA receptor (GABAR)-mediated HCO3- efflux, alkalinizing the cleft and disinhibiting cone CaV channels. This demonstrates how hybrid actions of GABA operate in parallel to effect voltage-dependent pH changes, a novel mechanism for regulating synaptic output.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.