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Record W4413883404 · doi:10.1016/j.isci.2025.113465

Toward biomimetic optogenetics: Drug-free activation of acute opiate reward

2025· article· en· W4413883404 on OpenAlexafffund
Lyla El-Fayomi, Hendrik W. Steenland, Michael Bergamini, Derek van der Kooy

Bibliographic record

VenueiScience · 2025
Typearticle
Languageen
FieldNeuroscience
TopicPhotoreceptor and optogenetics research
Canadian institutionsUniversity of Toronto
FundersCanadian Institutes of Health ResearchUniversity of Toronto
KeywordsOptogeneticsNeuroscienceDrugChemistryPharmacologyNanotechnologyMedicinePsychologyMaterials science

Abstract

fetched live from OpenAlex

to reflect context - we reconcile conflicting data on ventral tegmental area (VTA) GABA neurons in acute opiate reward. Activation using laser pulse sequences mimicking morphine-induced firing patterns is rewarding, while continuous light is aversive. When interspike intervals in rewarding morphine firing patterns are randomized, aversions also result, demonstrating the importance of temporal encoding in this system. We further establish the existence of VTA GABA projections to the tegmental pedunculopontine nucleus that drive reward in a dopamine-independent manner. Overall, our findings are consistent with non-optical studies characterizing VTA GABA neurons, and explain why previous optogenetic manipulations failed to corroborate those outcomes; proof-of-principle that temporal firing patterns are of critical importance in optogenetic toolkits.

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)0.000
metaresearch head score (Gemma)0.001
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 score0.015
Threshold uncertainty score0.504

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0000.000
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 head0.049
GPT teacher head0.343
Teacher spread0.294 · 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

Citations0
Published2025
Admission routes2
Has abstractyes

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