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Animals make decisions under the principle of reward value maximization and surprise minimization. It is still unclear how these principles are represented in the brain and are reflected in behavior. We addressed this question using a closed-loop virtual reality system to train adult zebrafish for active avoidance. Analysis of the neural activity of the dorsal pallium during training revealed neural ensembles assigning rules to the colors of the surrounding walls. Additionally, one third of fish generated another ensemble that becomes activated only when the real perceived scenery shows discrepancy from the predicted favorable scenery. The fish with the latter ensemble escape more efficiently than the fish with the former ensembles alone, even though both fish have successfully learned to escape, consistent with the hypothesis that the latter ensemble guides zebrafish to take action to minimize this prediction error. Our results suggest that zebrafish can use both principles of goal-directed behavior, but with different behavioral consequences depending on the repertoire of the adopted principles., Using a closed-loop virtual reality system for fish, the authors show that zebrafish are capable of assigning rules to the scenery they see, and of generating a state prediction error by comparing reality with a prediction derived from an internal model.

Optical measurement of membrane potentials enables fast, direct and simultaneous detection of membrane potentials from a population of neurons, providing a desirable approach for functional analysis of neuronal circuits. Here, we applied recently developed genetically encoded voltage indicators, ASAP1 (Accelerated Sensor of Action Potentials 1) and QuasAr2 (Quality superior to Arch 2), to zebrafish, an ideal model system for studying neurogenesis. To achieve this, we established transgenic lines which express the voltage sensors, and showed that ASAP1 is expressed in zebrafish neurons. To examine whether neuronal activity could be detected by ASAP1, we performed whole-cerebellum imaging, showing that depolarization was detected widely in the cerebellum and optic tectum upon electrical stimulation. Spontaneous activity in the spinal cord was also detected by ASAP1 imaging at single-cell resolution as well as at the neuronal population level. These responses mostly disappeared following treatment with tetrodotoxin, indicating that ASAP1 enabled optical measurement of neuronal activity in the zebrafish brain. Combining this method with other approaches, such as optogenetics and behavioural analysis may facilitate a deeper understanding of the functional organization of brain circuitry and its development.

The assembly of progenitor cells is a crucial step for organ formation during vertebrate development. Kupffer’s vesicle (KV) is a key organ required for the left-right asymmetric body plan in zebrafish, and is generated from a cluster of approximately 20 dorsal forerunner cells (DFCs). Although several genes are known to be involved in KV formation, how DFC clustering is regulated and how cluster formation then contributes to KV formation remain unclear. Here we show that positive feedback regulation of FGF signaling by Canopy1 (Cnpy1) controls DFC clustering without affecting DFC specification and DFC number. Cnpy1 positively regulates FGF signals within DFCs, which in turn promotes Cadherin1-mediated cell adhesion between adjacent DFCs to sustain cell cluster formation. When this FGF positive feedback loop is disrupted, the DFC cluster fails to form, eventually leading to KV malformation and defects in the establishment of laterality. Our results therefore uncover both a previously unidentified role of FGF signaling during vertebrate organogenesis and a regulatory mechanism underlying cell cluster formation, which is an indispensable step for formation of a functional KV and establishment of the left-right asymmetric body plan.