Summary Operant learning requires multiple cognitive processes, such as learning, prediction of potential outcomes, and decision-making. It is less clear how interactions of these processes lead to the behavioral adaptations that allow animals to cope with a changing environment. We show that juvenile zebrafish can perform conditioned place avoidance learning, with improving performance across development. Ablation of the dorsolateral habenula (dlHb), a brain region involved in associative learning and prediction of outcomes, leads to an unexpected improvement in performance and delayed memory extinction. Interestingly, the control animals exhibit rapid adaptation to a changing learning rule, whereas dlHb-ablated animals fail to adapt. Altogether, our results show that the dlHb plays a central role in switching animals’ strategies while integrating new evidence with prior experience.

Background: Odor-driven behaviors such as feeding, mating, and predator avoidance are crucial for animal survival. The neural pathways processing these behaviors have been well characterized in a number of species, and involve the activity of diverse brain regions following stimulation of the olfactory bulb by specific odors. However, while the zebrafish olfactory circuitry is well understood, a comprehensive characterization linking odor-driven behaviors to specific odors is needed to better relate olfactory computations to animal responses. Results: Here, we used a medium-throughput setup to measure the swimming trajectories of 10 zebrafish in response to 17 ecologically relevant odors. By selecting appropriate locomotor metrics, we constructed ethograms systematically describing odor-induced changes in the swimming trajectory. We found that adult zebrafish reacted to most odorants using different behavioral programs and that a combination of a few relevant behavioral metrics enabled us to capture most of the variance in these innate odor responses. We observed that individual components of natural food and alarm odors do not elicit the full behavioral response. Finally, we show that zebrafish blood elicits prominent defensive behaviors similar to those evoked by skin extract and activates spatially overlapping olfactory bulb domains. Conclusion: Altogether, our results highlight a prominent intra-and inter-individual variability in zebrafish odordriven behaviors and identify a small set of waterborne odors that elicit robust responses. Our behavioral setup and our results will be useful resources for future studies interested in characterizing innate olfactory behaviors in aquatic animals.

The developing brain undergoes drastic alterations. Here, we investigated developmental changes in the habenula, a brain region that mediates behavioral flexibility during learning, social interactions, and aversive experiences. We showed that developing habenular circuits exhibit multiple alterations that lead to an increase in the structural and functional diversity of cell types, inputs, and functional modules. As the habenula develops, it sequentially transforms into a multisensory brain region that can process visual, olfactory, mechanosensory, and aversive stimuli. Moreover, we observed that the habenular neurons display spatiotemporally structured spontaneous activity that shows prominent alterations and refinement with age. These alterations in habenular activity are accompanied by sequential neurogenesis and the integration of distinct neural clusters across development. Last, we revealed that habenular neurons with distinct functional properties are born sequentially at distinct developmental time windows. Our results highlight a strong link between the functional properties of habenular neurons and their precise birthdate.

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Operant conditioning requires multiple cognitive processes, such as learning, consolidation, prediction of potential outcomes and decision making. It is less clear how interactions of these processes led to behavioral adaptations that allows animal to cope with changing environment. We first showed that juvenile zebrafish can perform conditioned place avoidance learning, with improving performance across development. Next, we disentangled operant conditioning from contextual fear and anxiety. Our results revealed that animals' decisions and learning performance is shaped by the available information and animals' experience. Ablation of dorsal habenula (dHb), a brain region involved in learning and prediction of outcomes, led to an unexpected improvement in animals learning performance and delayed memory extinction. Interestingly, while the control animals' exhibit rapid adaptation to changing learning rules, dHb ablated animals failed to adapt. Altogether, our results showed that dHb plays a central role in switching animals' strategies while integrating new evidences with prior experience. Eggen, M. Andresen, V. Nguyen, A Nygard and our fish facility support team for technical assistance. We thank Nathalie Jurisch-Yaksi and Stephanie Fore for helpful comments on the text. We thank all Yaksi lab members for stimulating discussions. This work was funded by ERC starting grant 335561 (F.P., R.P., E.Y.) and RCN FRIPRO Research Grant 239973 (E.Y.). Work in the E.Y. lab is funded by the Kavli Institute for Systems Neuroscience at NTNU. AUTHOR CONTRIBUTIONSConceptualization, F.P., E.Y.; Methodology and data, F.P., B.S.; Recording software F.P., R.P.; Data