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Record W4413834068 · doi:10.1101/2025.08.28.672934

The Lateral Habenula to Ventral Tegmental Area Pathway is Required for Aversive Learning and Defensive Behaviors

2025· preprint· en· W4413834068 on OpenAlexafffund
Marina R. Ihidoype, Jose Cesar Hernandez Silva, Kelly-Ann Pellerin, Ekaterina Martian, Maryse Pinel, Christophe D. Proulx

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPlant-based Medicinal Research
Canadian institutionsUniversité LavalNanoQuébec (Canada)
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaConsejo Nacional de Ciencia y Tecnología
KeywordsVentral tegmental areaHabenulaPsychologyAversive StimulusNeuroscienceAvoidance learningCognitive psychologyDopamineCentral nervous system

Abstract

fetched live from OpenAlex

Summary The lateral habenula (LHb) provides aversive signals to the ventral tegmental area (VTA), but its contribution to learning and behavior remains poorly understood. Using a retrograde viral strategy, we targeted VTA-projecting LHb neurons and monitored calcium activity during active avoidance training. These neurons were activated by aversive stimuli and predictive cues as animals acquired avoidance responses and showed increased activity at movement onset during the tail suspension test (TST). Silencing LHb→VTA transmission impaired avoidance learning, prolonged escape latency, and reduced the persistence and vigor of active coping in the TST, without affecting baseline locomotion. Anatomical and ex vivo electrophysiology revealed that LHb terminals innervate both dopaminergic (TH⁺) and non-dopaminergic (TH⁻) VTA neurons, exhibiting session-specific synaptic adaptations during avoidance learning. Together, these findings identify the LHb→VTA pathway as a source of aversive predicting signals required for the acquisition of avoidance behavior and the persistence of active coping in aversive context. Highlights LHb→VTA neurons are required for aversive learning and adaptive avoidance These neurons respond to aversive stimuli, predictive cues, and movement onset Silencing the pathway impairs avoidance learning and reduces active coping in aversive contexts LHb→VTA inputs innervate DA and non-DA neurons and undergo learning-related plasticity

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.003
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.061
GPT teacher head0.371
Teacher spread0.310 · 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 source (direct Gemma or distilled Codex), 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".

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Citations0
Published2025
Admission routes2
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicPlant-based Medicinal ResearchFrench-language works237,207