Evidence map›Paper›PMID 41720091›Full record

ArticleNeuron2026

A hierarchical electrical synaptic circuit mechanism for integrative parallel visual processing in the retina.

Yao Xue, Yue Fei, Marcello DiStasio, Sean J Miller, Brian P Hafler, Liang Liang, Seunghoon Lee, Z Jimmy Zhou

Abstract read
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Yao XueDepartments of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA; Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA.
Yue FeiInterdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
Marcello DiStasioDepartments of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA; Wu Tsai Institute, Yale University School of Medicine, New Haven, CT, USA.
Sean J MillerDepartments of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA.
Brian P HaflerDepartments of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA; Wu Tsai Institute, Yale University School of Medicine, New Haven, CT, USA.
Liang LiangDepartment of Neuroscience, Yale University School of Medicine, New Haven, CT, USA; Wu Tsai Institute, Yale University School of Medicine, New Haven, CT, USA.
Seunghoon LeeDepartments of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA. Electronic address: seunghoon.lee@yale.edu.
Z Jimmy ZhouDepartments of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA; Wu Tsai Institute, Yale University School of Medicine, New Haven, CT, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA. Electronic address: jimmy.zhou@yale.edu.

Funding

Yale Core Grant for Vision ResearchP30EY026878 · NEI · YALE UNIVERSITY · PI In-Jung Kim · 2016 to 2026
$7.1M
Synaptic mechanisms and circuitry of retinal interneuronsR01EY034652 · NEI · YALE UNIVERSITY · PI Z JIMMY ZHOU · 2023 to 2026
$2.1M
Targeting the inflammatory response in age-related macular degenerationR01EY034234 · NEI · YALE UNIVERSITY · PI Brian P Hafler · 2022 to 2026
$2.0M
Functional circuitry and computation of the visual thalamusR01EY034697 · NEI · YALE UNIVERSITY · PI Liang Liang · 2023 to 2026
$1.6M
Physiology and Organization of Retinal Cell TypesR01EY036472 · NEI · YALE UNIVERSITY · PI ZHOU, Z JIMMY · 2025 to 2025
$1.6M
NEI NIH HHS P30 EY026878NEI NIH HHS R01 EY034234NEI NIH HHS R01 EY034652NEI NIH HHS R01 EY034697NEI NIH HHS R01 EY036472
6 · The paper itself

Abstract

Parallel visual processing begins with retinal bipolar cells, traditionally regarded as independent chemical synaptic channels. However, the circuit-level synaptic integration of chemical and electrical synapses within this network remains unclear. Using dual patch-clamp recordings and two-photon imaging in whole-mount retina, we systematically characterized synaptic transmission across 13 mouse and 2 human cone bipolar cell (CBC) types, revealing two distinct modes: a fast, direct chemical pathway and a slower, serial electrical-chemical circuit among both ON and OFF CBCs. In mice, the slow mode generates spatially dispersed glutamate "clouds" that facilitate integration across CBC types. We discovered specific "driver" CBCs that distribute robust, sustained signals through a hierarchical, functionally rectified network, enhancing sensitivity to small, low-contrast stimuli in downstream retinal cells and thalamic neurons in awake mice. Our findings challenge the classical view of independent CBC channels, revealing an integrative, hierarchical electrical-chemical synaptic architecture that enhances visual detection and coding efficiency.

Indexed as

Electrical SynapsesRetinaRetinal Bipolar CellsSynaptic TransmissionVisual PathwaysAnimalsGlutamic AcidHumansMiceMice, Inbred C57BLPatch-Clamp TechniquesPhotic StimulationGlutamic Aciddriver cellsdual patch clampgap-junctional synaptic transmissionglutamate cloudin vivo Ca imaging in dLGNparallel visual processingpostmortem human retinaretinal bipolar cellstransient and sustained light responsestwo-photon glutamate imaging

Identifiers

PMID41720091
PMCPMC12927596

What OpenQuestion holds

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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.