Modulation of habenula axon terminals supports action-outcome associations in larval zebrafish.

Authors

Emanuele Paoli, Virginia Palieri, Amey Shenoy, Ruben Portugues

Published in

Nature communications. Volume 17. Issue 1. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

Improving behavioral performance relies on the ability to associate decisions with their positive and negative outcomes. Although neurons that associate actions with their consequences have been identified across multiple brain regions, the circuit-level mechanisms underlying this integration remain poorly understood. Here, using an operant thermoregulatory assay in larval zebrafish, we show that the dorsal habenula-interpeduncular nucleus (dHb-IPN) pathway is necessary for associating actions with subsequent thermal reward. A population of intermediate IPN (iIPN) neurons encodes actions only when they lead to reward, suggesting a role in establishing action-outcome associations. This integration is temporally precise, requiring actions and their outcomes to occur within approximately one second in both the behavioral assay and iIPN responses. We then combine circuit mapping and axon imaging to show that actions and reward signals are conveyed by GABAergic prepontine and glutamatergic dHb neurons, respectively. Finally, the integration between action and reward signals relies on presynaptic GABA_B receptor-mediated modulation of dHb axon terminals by prepontine neurons. These results link a crucial computation for adaptive behavior to a specific circuit mechanism.

PMID:
42575891
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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