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

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, we show that larval zebrafish maintain a short-term memory of action-outcome associations and that the dorsal habenula-interpeduncular nucleus (dHb–IPN) pathway is necessary for this process. Consistently, a population of intermediate IPN neurons encodes actions only when they lead to a thermal reward, suggesting a major role in establishing short-term associations and influencing subsequent decisions. 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 motor and sensory streams relies on presynaptic GABA_Breceptor–mediated modulation of dHb axon terminals by prepontine neurons.

These results link a crucial computation for adaptive behavior to a specific circuit mechanism.