Segregated glycine-glutamate co-transmission from vGluT3 amacrine cells to contrast-suppressed and contrast-enhanced retinal circuits
Open accessAbstract
Since the introduction of Dale's principle of "one neuron releases one transmitter at all its synapses," a growing number of exceptions to this principle have been identified. While the concept of neurotransmitter co-release by a single neuron is now well accepted, the specific synaptic circuitry and functional advantage of co-neurotransmission remain poorly understood in general. Here we report Ca(2+)-dependent co-release of a new combination of inhibitory and excitatory neurotransmitters, namely, glycine and glutamate, by the vGluT3-expressing amacrine cell (GAC) in the mouse retina. GACs selectively make glycinergic synapses with uniformity detectors (UDs) and provide a major inhibitory drive that underlies the suppressed-by-contrast trigger feature of UDs. Meanwhile, GACs release glutamate to excite OFF alpha ganglion cells and a few other nonlinear, contrast-sensitive ganglion cells. This coordinated inhibition and excitation of two separate neuronal circuits by a single interneuron suggests a unique advantage in differential detection of visual field uniformity and contrast.
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vGluT3+ retinal amacrine cells release both glycine and glutamate onto separate populations of retinal ganglion cells.
“a class of vGluT3+ retinal amacrine cells was recently found to release both the inhibitory neurotransmitter glycine and excitatory neurotransmitter glutamate onto distinct populations of retinal ganglion cells (RGCs).99,100”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [99]
Glutamatergic synapses from vGluT3+ amacrine cells target OFF alpha ganglion cells and other retinal cell types but avoid suppressed-by-contrast RGCs.
“Glutamatergic synapses from vGluT3+ retinal amacrine cells are more promiscuous and target OFF alpha ganglion cells and other retinal cell types but avoid suppressed by contrast RGCs.99”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [99]
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Root, D. H., Zhang, S., Barker, D. J., Miranda-Barrientos, J., Liu, B., Wang, H.-L., & Morales, M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.05.063 · Cited by 153 · see citing works
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Synaptic and circuit functions of multitransmitter neurons in the mammalian brain
Wallace, M. L., & Sabatini, B. L. (2023) · Neuron · doi:10.1016/j.neuron.2023.06.003 · Cited by 59 · see citing works
- Authors
- Lee, S., Zhang, Y., Chen, M., & Zhou, Z. J.
- Affiliations
- Sichuan University (CN)
- Yale University (US)
- Corresponding author
- Zhou, Z. Jimmy
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 90
- Issue
- 1
- Pages
- 27-34
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4824647
- OpenAlex
- W2300106671
- Cited by
- 101
- References
- 27
- Citations by year
- 2026: 10 · 2025: 5 · 2024: 7 · 2023: 11 · 2022: 7 · 2021: 15 · 2020: 13 · 2019: 7 · 2018: 7 · 2017: 13 · 2016: 6
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Research to Prevent Blindness
- Yale University
- China Scholarship Council
- National Institutes of Health
- National Eye Institute (EY026065, R01EY026065, EY017353, P30EY000785, R01EY017353, P30EY026878)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
- Keywords
- contrast enhancement, retinal circuitry, Dale's principle, retinal interneurons
- MeSH terms
- Animals, Calcium, Glycine, Neural Inhibition, Synaptic Transmission, Retina, Retinal Ganglion Cells, Synapses, Visual Fields, Patch-Clamp Techniques, Glutamic Acid, Amacrine Cells, Amino Acid Transport Systems, Acidic, Mice
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