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Record W7116883566 · doi:10.1038/s41592-025-02965-z

Glutamate indicators with increased sensitivity and tailored deactivation rates

2025· article· en· W7116883566 on OpenAlexaff
Abhi Aggarwal, Adrian Negrean, Yang Chen, Rishyashring R. Iyer, Daniel Reep, Anyi Liu, Anirudh Palutla, Michael E. Xie, Bryan MacLennan, Kenta M. Hagihara, Lucas W. Kinsey, Julianna L. Sun, Pantong Yao, Arthur Tsang, Getahun Tsegaye, Yonghai Zhang, Ronak Patel, Benjamin J. Arthur, Julien Hiblot, Philipp Leippe, Mirosław Tarnawski, Jonathan S. Marvin, Jason Vevea, Srinivas C. Turaga, Alison G. Tebo, Matteo Carandini, L. Federico Rossi, David Kleinfeld, Arthur Konnerth, Karel Svoboda, Glenn Turner, Jeremy P. Hasseman, Kaspar Podgorski

Bibliographic record

VenueNature Methods · 2025
Typearticle
Languageen
FieldNeuroscience
TopicNeuroscience and Neuropharmacology Research
Canadian institutionsLibin Cardiovascular Institute of AlbertaUniversity of Calgary
FundersBiotechnology and Biological Sciences Research CouncilBoehringer Ingelheim StiftungNational Institutes of HealthHuman Frontier Science ProgramDeutsche ForschungsgemeinschaftUK Research and InnovationAmerican Lebanese Syrian Associated CharitiesGiovanni Armenise-Harvard FoundationPaul and Daisy Soros Fellowships for New AmericansHoward Hughes Medical Institute
KeywordsGlutamate receptorNeurotransmissionSensitivity (control systems)Hippocampal formationNeural activityFluorescenceInformation transmission

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.029
Threshold uncertainty score0.447

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.024
GPT teacher head0.430
Teacher spread0.406 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7
Published2025
Admission routes1
Has abstractyes

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