Evidence map›Paper›PMID 40251167›Full record

ArticleNature communications2025

Molecular mechanism establishing the OFF pathway in vision.

Florentina Soto, Chin-I Lin, Andrew Jo, Ssu-Yu Chou, Ellen G Harding, Philip A Ruzycki, Gail K Seabold, Ronald S Petralia, Daniel Kerschensteiner

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Protocadherin 9 Promotes Cell Survival of Different Bipolar Cell Types in the Developing Mouse Retina.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Florentina SotoDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA. sotof@wustl.edu.ORCID http://orcid.org/0000-0003-4106-8119
Chin-I Lin *Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9170-4403
Andrew Jo *Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
Ssu-Yu ChouDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-7496-5185
Ellen G HardingDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
Philip A RuzyckiDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-3520-6407
Gail K SeaboldLaboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
Ronald S PetraliaLaboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.
Daniel KerschensteinerDepartment of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA. kerschensteinerd@wustl.edu.ORCID http://orcid.org/0000-0002-6794-9056

Funding

WASHINGTON UNIVERSITY CENTER VISION RESEARCHP30EY002687 · NEI · WASHINGTON UNIVERSITY · PI Philip Andrew Ruzycki · 1985 to 2026
$18.4M
Research Training Program in the Vision SciencesT32EY013360 · NEI · WASHINGTON UNIVERSITY · PI SHIMING CHEN, Daniel Kerschensteiner · 2000 to 2026
$5.6M
SYNAPTIC ORGANIZATION AND VISUAL PROCESSING IN INTERNEURON CIRCUITS OF THE RETINAR01EY026978 · NEI · WASHINGTON UNIVERSITY · PI Daniel Kerschensteiner · 2016 to 2026
$3.8M
Synapse rescue and neuroprotection in the retinaR01EY027411 · NEI · WASHINGTON UNIVERSITY · PI Daniel Kerschensteiner · 2017 to 2026
$3.4M
Visual pathway cooperation to align viewing strategies and processing specializations for predationR01EY034001 · NEI · WASHINGTON UNIVERSITY · PI Daniel Kerschensteiner · 2022 to 2026
$2.0M
NEI NIH HHS P30 EY002687NEI NIH HHS R01 EY026978NEI NIH HHS R01 EY027411NEI NIH HHS R01 EY034001NEI NIH HHS T32 EY013360U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) EY026978U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) EY034001
6 · The paper itself

Abstract

Parallel ON and OFF (positive- and negative-contrast) pathways fundamental to vision arise at the complex synapse of cone photoreceptors. Cone pedicles form spatially segregated functionally opposite connections with ON and OFF bipolar cells. Here, we discover that mammalian cones express LRFN2, a cell-adhesion molecule, which localizes to the pedicle base. LRFN2 stabilizes basal contacts between cone pedicles and OFF bipolar cell dendrites to guide pathway-specific partner choices, encompassing multiple cell types. In addition, LRFN2 trans-synaptically organizes glutamate receptor clusters, determining the contrast preferences of the OFF pathway. ON and OFF pathways converge in the inner retina to regulate bipolar cell outputs. We analyze LRFN2's contributions to ON-OFF interactions, pathway asymmetries, and neural and behavioral responses to approaching predators. Our results reveal that LRFN2 controls the formation of the OFF pathway in vision, supports parallel processing in a single synapse, and shapes contrast coding and the detection of visual threats.

Indexed as

Retinal Cone Photoreceptor CellsVision, OcularVisual PathwaysAnimalsCell Adhesion MoleculesDendritesHumansMiceMice, Inbred C57BLReceptors, GlutamateRetinaRetinal Bipolar CellsSynapsesCell Adhesion MoleculesReceptors, Glutamate

Identifiers

PMID40251167
PMCPMC12008213

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.