A zebrafish circuit for behavioral credit assignment

Background:

Learning to associate an action with its outcome, “credit assignment”, is a fundamental challenge for all brains. In both natural and artificial systems, the problem is how to pinpoint which neuronal circuit elements deserve credit (or blame) for a successful or failed action. Classic studies in dopamine signalling and prediction error paved the way for understanding reinforcement learning ¹. In mammals, the lateral orbitofrontal cortex (lOFC) and hippocampus (HC) are known to form abstract representations that help assign credit to specific choices, even when the feedback is delayed ^2,3.

Recent theoretical and experimental advances have begun to unravel the cellular and circuit-level mechanisms underlying this process. In zebrafish, a vertebrate model that enables optical and genetic access to neural circuits, researchers have identified a key pathway for credit assignment: the dorsal habenula (dHb) to interpeduncular nucleus (IPN) circuit (see Fig.1) ^4,5.

This pathway is particularly intriguing because it is lateralized. The right dHb, enriched for neurons expressing the lratd2a gene, receives bilateral olfactory input from mitral cells and selectively projects to a defined region of the IPN ^6,7. Such asymmetry is not unique to zebrafish; lateralized processing of sensory cues is observed in bees⁸, rodents⁹ and humans ¹⁰. Thus, deciphering how the right dHb integrates sensory (e.g. olfactory, visual etc) cues with motor actions may illuminate a conserved mechanism by which vertebrate brains assign credit.

In the present preprint ⁴, the authors combine innovative operant behavioral assays with calcium imaging, chemogenetic manipulations, and detailed circuit reconstructions (Fig. 1) to show that adaptive responses in zebrafish require a precise temporal coupling between an action (a turn) and its sensory feedback (temperature change). Notably, they demonstrate that the dHb–IPN circuit uses GABAB receptor–mediated presynaptic modulation to “multiply” sensory and choice signals effectively marking the synapses that contributed to a successful action ^11,12.

 

Fig. 1 – Anatomical reconstructions and circuit organization (a–h) illustrating the connectivity of dorsal habenula (dHb) axons with glomerular inhibitory interpeduncular nucleus (iIPN) neurons. Fig. 3 of the preprint highlighted here, made available under a CC-BY-NC-ND 4.0 International license.

 

Key Findings:

Temporal Coupling is Essential:

Using an operant thermoregulatory assay, the authors showed that zebrafish must execute a turn and then receive a temperature boost (tempUP) within a narrow time window to reduce exposure to cold. Delays disrupted this credit assignment process, indicating that precise timing is crucial for learning which actions lead to positive outcomes.

Circuit Specificity – The dHb–IPN Pathway:

Through chemogenetic ablations, the authors demonstrated that the dorsal habenula—particularly its right subregion rich in lratd2a-expressing neurons—is essential for adaptive behavior. Although these neurons are not required for innate temperature responses, they are indispensable for experience-dependent behavioral adjustments.

Multiplicative Integration via GABAB Modulation:

Functional imaging revealed that neurons in the intermediate IPN act as coincidence detectors: they produced a robust, multiplicative-like response only when a specific turn was closely followed by a temperature increase. Pharmacological blockade of GABAB receptors abolished these responses, underscoring their role in presynaptic modulation of dHb axon terminals.

Lateralization and Generalization:

The asymmetry observed in the zebrafish dHb mirrors lateralized processing seen in other species. This not only reinforces the importance of the right dHb in linking actions to outcomes, but also suggests that similar circuit-level solutions may be used across vertebrates for credit assignment in both olfactory and other sensory modalities.

 

Why I highlight this preprint?

This paper elegantly dissects the circuit-level mechanisms underlying credit assignment, an essential computation for adaptive behavior, by combining innovative operant assays with high-resolution imaging and chemogenetic manipulations in zebrafish. I really appreciate the way in which the study convincingly describes a precise temporal integration of motor actions with sensory feedback via the dorsal habenula–interpeduncular pathway, highlighting the role of presynaptic GABAB receptor modulation. This multidisciplinary approach not only deepens our understanding of neural computations but also offers a compelling framework for exploring similar mechanisms across vertebrates, aligning perfectly with my research interests in unraveling the neural basis of adaptive behavior.

 

Questions for the authors:

1. Can the same dHb–IPN circuit mechanism support credit assignment for other sensory feedback modalities (e.g., visual or auditory cues), or is it specialized for thermosensory inputs?
2. Given the critical dependence on precise timing between an action and its feedback, how sensitive is the circuit to small variations in the action–outcome interval, and what cellular mechanisms might ensure that this narrow temporal window is maintained?
3. Since dHb ablation impairs adaptive responses but spares innate temperature reactions, how do you envision the dHb differentially integrating experience-dependent signals compared to hardwired sensorimotor circuits?

 

References:

1. Schultz, W., Dayan, P., & Montague, P. R. (1997). A neural substrate of prediction and reward. Science, 275(5306), 1593-1599.
2. Boorman, E. D., Behrens, T. E., & Rushworth, M. F. (2011). Counterfactual choice and learning in a neural network centered on human lateral frontopolar cortex. PLoS biology, 9(6), e1001093.
3. Jocham, G., Klein, T. A., & Ullsperger, M. (2011). Dopamine-mediated reinforcement learning signals in the striatum and ventromedial prefrontal cortex underlie value-based choices. Journal of Neuroscience, 31(5), 1606-1613.
4. Paoli, E., Palieri, V., Shenoy, A., & Portugues, R. (2025). A zebrafish circuit for behavioral credit assignment. bioRxiv, 2025-02.
5. Cherng, B. W., Islam, T., Torigoe, M., Tsuboi, T., & Okamoto, H. (2020). The dorsal lateral habenula-interpeduncular nucleus pathway is essential for left-right-dependent decision making in zebrafish. Cell reports, 32(11).
6. Miyasaka, N., Arganda-Carreras, I., Wakisaka, N., Masuda, M., Sümbül, U., Seung, H. S., & Yoshihara, Y. (2014). Olfactory projectome in the zebrafish forebrain revealed by genetic single-neuron labelling. Nature communications, 5(1), 3639.
7. Decarvalho, T. N., Akitake, C. M., Thisse, C., Thisse, B., & Halpern, M. E. (2013). Aversive cues fail to activate fos expression in the asymmetric olfactory-habenula pathway of zebrafish. Frontiers in neural circuits, 7, 98.
8. Rogers, L. J., & Vallortigara, G. (2008). From antenna to antenna: lateral shift of olfactory memory recall by honeybees. PLoS One, 3(6), e2340.
9. Sakaguchi, Y., & Sakurai, Y. (2017). Left–right functional asymmetry of ventral hippocampus depends on aversiveness of situations. Behavioural Brain Research, 325, 25-33.
10. Avram, J., Balteş, F. R., Miclea, M., & Miu, A. C. (2010). Frontal EEG activation asymmetry reflects cognitive biases in anxiety: evidence from an emotional face Stroop task. Applied psychophysiology and biofeedback, 35, 285-292.
11. Amo, R., Fredes, F., Kinoshita, M., Aoki, R., Aizawa, H., Agetsuma, M., … & Okamoto, H. (2014). The habenulo-raphe serotonergic circuit encodes an aversive expectation value essential for adaptive active avoidance of danger. Neuron, 84(5), 1034-1048.
12. Noonan, M. P., Chau, B. K., Rushworth, M. F., & Fellows, L. K. (2017). Contrasting effects of medial and lateral orbitofrontal cortex lesions on credit assignment and decision-making in humans. Journal of Neuroscience, 37(29), 7023-7035.

Tags: sensory processing, systems neuroscience

doi: https://doi.org/10.1242/prelights.39753

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