Evidence map›Paper›PMID 41436654›Full record

ArticleNature methods2026

Glutamate indicators with increased sensitivity and tailored deactivation rates.

Abhi Aggarwal, Adrian Negrean, Yang Chen, Rishyashring Iyer, Daniel Reep, Anyi Liu, Anirudh Palutla, Michael E Xie, Bryan J MacLennan, Kenta M Hagihara and 24 more

Abstract read
In one paragraph

Article in Nature methods, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Tuft Dendrite Spikes Are Accompanied by Selective Input From Distinct Functional Networks.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors.

Abhi Aggarwal *Allen Institute for Neural Dynamics, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-6336-566X
Adrian Negrean *Allen Institute for Neural Dynamics, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-9256-7412
Yang Chen *Institute of Neuroscience and Munich Cluster for Systems Neurology, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-6774-3007
Rishyashring Iyer *Department of Physics, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9126-9491
Daniel ReepJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.ORCID http://orcid.org/0009-0009-7638-9538
Anyi LiuUniversity College London, London, UK.
Anirudh PalutlaJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.ORCID http://orcid.org/0009-0000-3997-4943
Michael E XieAllen Institute for Neural Dynamics, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-4026-9181
Bryan J MacLennanAllen Institute for Neural Dynamics, Seattle, WA, USA.
Kenta M HagiharaAllen Institute for Neural Dynamics, Seattle, WA, USA.
Lucas W KinseyAllen Institute for Neural Dynamics, Seattle, WA, USA.
Julianna L SunNeuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Pantong YaoDepartment of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Jihong ZhengJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.ORCID http://orcid.org/0000-0002-1247-6087
Arthur TsangJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Getahun TsegayeJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Yonghai ZhangInstitute of Neuroscience and Munich Cluster for Systems Neurology, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0009-0004-6121-427X
Ronak H PatelJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Benjamin J ArthurJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.ORCID http://orcid.org/0000-0003-3545-8807
Julien HiblotMax Planck Institute for Medical Research, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-7883-8079
Philipp LeippeCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Wien, Austria.
Miroslaw TarnawskiMax Planck Institute for Medical Research, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-5297-5668
Jonathan S MarvinJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.ORCID http://orcid.org/0000-0003-2294-4515
Jason D VeveaNeuronal Cell Biology Division, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Srinivas C TuragaJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.ORCID http://orcid.org/0000-0003-3247-6487
Alison G TeboJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.ORCID http://orcid.org/0000-0003-0788-5617
Matteo CarandiniUniversity College London, London, UK.ORCID http://orcid.org/0000-0003-4880-7682
L Federico RossiUniversity College London, London, UK.ORCID http://orcid.org/0000-0001-5831-4860
David KleinfeldDepartment of Physics, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9797-4722
Arthur KonnerthInstitute of Neuroscience and Munich Cluster for Systems Neurology, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-9548-2676
Karel SvobodaAllen Institute for Neural Dynamics, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-6670-7362
Glenn C TurnerJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.ORCID http://orcid.org/0000-0002-5341-2784
Jeremy P HassemanJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. hassemanj@janelia.hhmi.org.ORCID http://orcid.org/0000-0002-0096-7321
Kaspar PodgorskiAllen Institute for Neural Dynamics, Seattle, WA, USA. kaspar.podgorski@alleninstitute.org.ORCID http://orcid.org/0000-0002-0374-2005

Funding

Top-down and bottom-up signals for flexible orofacial behaviorsU19NS137920 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Beth Friedman · 2024 to 2026
$15.9M
Optimization of genetically encoded voltage and neurotransmitter indicators for multiwavelength in vivo analysis of brain circuitsUM1MH136462 · NIMH · MAX PLANCK FLORIDA CORPORATION · PI Michael Z. Lin, Kaspar Podgorski · 2024 to 2026
$6.3M
Optimization of Calcium and RNA multiplexed activity imaging for highly parallelized evaluation of cell type functions in deep-brain structuresU01NS126054 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CUI, MENG, STERNSON, SCOTT M · 2022 to 2025
$3.0M
Measuring input-output operations of cortical neurons with large-scale neurotransmitter imagingDP2NS136990 · NINDS · ALLEN INSTITUTE · PI Kaspar Podgorski · 2023 to 2026
$2.5M
Imaging the molecular constituents of the brain vasculature and lymphatic connectomeU24EB028942 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KLEINFELD, DAVID · 2019 to 2024
$1.8M
CRCNS : Thalamocortical vs. recurrent connectivity in active sensation of vibrissa touchR01NS143141 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI David Kleinfeld · 2025 to 2026
$551k
STUDYING SINGLE NEURON COMPUTATIONS WITHIN BRAIN-WIDE CIRCUITSF30MH138009 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Michael Everest Xie · 2024 to 2026
$164k
Deutsche Forschungsgemeinschaft (German Research Foundation) KO 979/7-1Human Frontier Science Program (HFSP) T0052/2022-LNIBIB NIH HHS U24 EB028942NIMH NIH HHS F30 MH138009NIMH NIH HHS UM1 MH136462NINDS NIH HHS DP2 NS136990NINDS NIH HHS R01 NS143141NINDS NIH HHS U01 NS126054NINDS NIH HHS U19 NS137920U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1DP2NS136990U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1F30MH138009U.S. Department of Health & Human Services | National Institutes of Health (NIH) U01 NS12605U.S. Department of Health & Human Services | National Institutes of Health (NIH) UM1MH136462
6 · The paper itself

Abstract

Understanding how neurons integrate signals from thousands of input synapses requires methods to monitor neurotransmission across many sites simultaneously. The fluorescent protein glutamate indicator iGluSnFR enables visualization of synaptic signaling, but the sensitivity, scale and speed of such measurements are limited by existing variants. Here we developed two highly sensitive fourth-generation iGluSnFR variants with fast activation and tailored deactivation rates: iGluSnFR4f for tracking rapid dynamics, and iGluSnFR4s for recording from large populations of synapses. These indicators detect glutamate with high spatial specificity and single-vesicle sensitivity in vivo. We used them to record natural patterns of synaptic transmission across multiple experimental contexts in mice, including two-photon imaging in cortical layers 1-4 and hippocampal CA1, and photometry in the midbrain. The iGluSnFR4 variants extend the speed, sensitivity and scalability of glutamate imaging, enabling direct observation of information flow through neural networks in the intact brain.

Indexed as

Glutamic AcidSynaptic TransmissionAnimalsLuminescent ProteinsMiceMice, Inbred C57BLNeuronsSynapsesGlutamic AcidLuminescent Proteins

Identifiers

PMID41436654
PMCPMC12904790

What Socratic 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 Socratic graph.