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To make appropriate decisions, animals need to accumulate sensory evidence. Simple integrator models can explain many aspects of such behavior, but how the underlying computations are mechanistically implemented in the brain remains poorly understood. Here we approach this problem by adapting the random-dot motion discrimination paradigm, classically used in primate studies, to larval zebrafish. Using their innate optomotor response as a measure of decision making, we find that larval zebrafish accumulate and remember motion evidence over many seconds and that the behavior is in close agreement with a bounded leaky integrator model. Through the use of brain-wide functional imaging, we identify three neuronal clusters in the anterior hindbrain that are well suited to execute the underlying computations. By relating the dynamics within these structures to individual behavioral choices, we propose a biophysically plausible circuit arrangement in which an evidence integrator competes against a dynamic decision threshold to activate a downstream motor command.

Navigating across light gradients is essential for survival for many animals. However, we still have a poor understanding of the algorithms that underlie such behaviors. Here, we developed a novel closed-loop phototaxis assay for Drosophila larvae in which light intensity is always spatially uniform but updates depending on the location of the animal in the arena. Even though larvae can only rely on temporal cues during runs, we find that they are capable of finding preferred areas of low light intensity. Further detailed analysis of their behavior reveals that larvae turn more frequently and that heading angle changes increase when they experience brightness increments over extended periods of time. We suggest that temporal integration of brightness change during runs is an important – and so far largely unexplored – element of phototaxis.

SUMMARYTo thrive, organisms must maintain physiological and environmental variables in optimal ranges. However, in a dynamic world, the optimal range of a variable might fluctuate depending on the organism’s state or environmental conditions. Given these fluctuations, how do biological control systems maintain optimal control of physiological and environmental variables? We explored this question by studying the phototactic behavior of larval zebrafish. We demonstrate, with behavioral experiments and computational modeling, that larval zebrafish use phototaxis to maintain environmental luminance at a set point that depends on luminance history. We further show that fish compute this set point using information from both eyes, and that the set point fluctuates on a timescale of seconds when environmental luminance changes. These results expand on previous studies, where phototaxis was found to be primarily positive, and suggest that larval zebrafish, rather than consistently turning towards the brighter areas, exert homeostatic control over the luminance of their surroundings. Furthermore, we show that fluctuations in the surrounding luminance feed back on the system to drive allostatic changes to the luminance set point. Our work has uncovered a novel principle underlying phototaxis in larval zebrafish and characterized a behavioral algorithm by which larval zebrafish exert control over a sensory variable.

Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. Here we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs., eLife digest How soon after a meal do you start feeling hungry again? The answer depends on a complex set of processes within the brain that regulate appetite. A key player in these processes is the hypothalamus, a small structure at the base of the brain. The hypothalamus consists of many different subregions, some of which are responsible for increasing or decreasing hunger. Wee, Song et al. now show how two of these subregions interact to regulate appetite and feeding, by studying them in hungry zebrafish larvae. The brains of zebrafish have many features in common with the brains of mammals, but they are smaller and transparent, which makes them easier to study. Wee, Song et al. show that as larvae become hungry, an area called the caudal hypothalamus increases its activity. But when the larvae find food and start feeding, activity in this area falls sharply. It then remains low while the hungry larvae eat as much as possible. Eventually the larvae become full and start eating more slowly. As they do so, the activity of the caudal hypothalamus goes back to normal levels. While this is happening, activity in a different area called the lateral hypothalamus shows the opposite pattern. It has low activity in hungry larvae, which increases when food becomes available and feeding begins. When the larvae finally reduce their rate of feeding, the activity in the lateral hypothalamus drops back down. The authors posit that by inhibiting each other’s activity, the caudal and lateral hypothalamus work together to ensure that animals search for food when necessary, but switch to feeding behavior when food becomes available. Serotonin – which is produced by the caudal hypothalamus – and drugs that act like it have been proposed to suppress appetite, but they have varied and complex effects on food intake and weight gain. By showing that activity in the caudal hypothalamus changes depending on whether food is present, the current findings may provide insights into this complexity. More generally, they show that mapping the circuits that regulate appetite and feeding in simple organisms could help us understand the same processes in humans.

The reliable estimation of motion across varied surroundings represents a survival-critical task for sighted animals. How neural circuits have adapted to the particular demands of natural environments, however, is not well understood. We explored this question in the visual system of Drosophila melanogaster. Here, as in many mammalian retinas, motion is computed in parallel streams for brightness increments (ON) and decrements (OFF). When genetically isolated, ON and OFF pathways proved equally capable of accurately matching walking responses to realistic motion. To our surprise, detailed characterization of their functional tuning properties through in vivo calcium imaging and electrophysiology revealed stark differences in temporal tuning between ON and OFF channels. We trained an in silico motion estimation model on natural scenes and discovered that our optimized detector exhibited differences similar to those of the biological system. Thus, functional ON-OFF asymmetries in fly visual circuitry may reflect ON-OFF asymmetries in natural environments.

Many animals rely on vision to detect, locate, and track moving objects. In Drosophila courtship, males primarily use visual cues to orient toward and follow females and to select the ipsilateral wing for courtship song. Here, we show that the LC10 visual projection neurons convey essential visual information during courtship. Males with LC10 neurons silenced are unable to orient toward or maintain proximity to the female and do not predominantly use the ipsilateral wing when singing. LC10 neurons preferentially respond to small moving objects using an antagonistic motion-based center-surround mechanism. Unilateral activation of LC10 neurons recapitulates the orienting and ipsilateral wing extension normally elicited by females, and the potency with which LC10 induces wing extension is enhanced in a state of courtship arousal controlled by male-specific P1 neurons. These data suggest that LC10 is a major pathway relaying visual input to the courtship circuits in the male brain.