Mechanisms of simultaneous linear and nonlinear computations at the mammalian cone photoreceptor synapse

Chad P. Grabner, Daiki Futagi, Jun Shi, Vytas Bindokas, Katsunori Kitano, Eric A. Schwartz, Steven H. DeVries*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Neurons enhance their computational power by combining linear and nonlinear transformations in extended dendritic trees. Rich, spatially distributed processing is rarely associated with individual synapses, but the cone photoreceptor synapse may be an exception. Graded voltages temporally modulate vesicle fusion at a cone’s ~20 ribbon active zones. Transmitter then flows into a common, glia-free volume where bipolar cell dendrites are organized by type in successive tiers. Using super-resolution microscopy and tracking vesicle fusion and postsynaptic responses at the quantal level in the thirteen-lined ground squirrel, Ictidomys tridecemlineatus, we show that certain bipolar cell types respond to individual fusion events in the vesicle stream while other types respond to degrees of locally coincident events, creating a gradient across tiers that are increasingly nonlinear. Nonlinearities emerge from a combination of factors specific to each bipolar cell type including diffusion distance, contact number, receptor affinity, and proximity to glutamate transporters. Complex computations related to feature detection begin within the first visual synapse.

Original languageEnglish (US)
Article number3486
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

Funding

This work was supported NIH R01 EY012141, an unrestricted grant to the Dept of Ophthalmology from Research to Prevent Blindness, an International Travel Award from RPB (S.H.D.), and JSPS KAKENHI grant #19H01140 (K.K. and D.F.). Imaging and data analysis was performed at the University of Chicago Integrated Light Microscopy Core RRID: SCR_019197. We wish to thank Raina DeVries (University of Chicago) for 3D surfacing of super-resolution images, Peter Sterling (University of Pennsylvania) for helpful comments on the manuscript, and Yongling Zhu (Northwestern University) for AAV manufacture. This work was supported NIH R01 EY012141, an unrestricted grant to the Dept of Ophthalmology from Research to Prevent Blindness, an International Travel Award from RPB (S.H.D.), and JSPS KAKENHI grant #19H01140 (K.K. and D.F.). Imaging and data analysis was performed at the University of Chicago Integrated Light Microscopy Core RRID: SCR_019197. We wish to thank Raina DeVries (University of Chicago) for 3D surfacing of super-resolution images, Peter Sterling (University of Pennsylvania) for helpful comments on the manuscript, and Yongling Zhu (Northwestern University) for AAV manufacture.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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