Modulation of visual processing by the Melanocortin system in Larval Zebrafish
1 RTG-NCA|GRK 1960, Institute of Zoology, University of Cologne, Cologne, Germany
2 Werner Reichardt Centre for Integrative Neuroscience, Tuebingen, Germany
3 Max Planck Institute for Neurobiology of Behavior u2013 caesar, Bonn, Germany
4 Department of Neurology, University Hospital Cologne, Cologne, Germany
5 Institute of Zoology, University of Cologne, Cologne, Germany
Animals regulate a balance between energy intake and expenditure in order to survive and accommodate their physiological energy needs. At the core of this energy homeostasis control lies the hypothalamic melanocortin system. Like mammals, appetite and energy homeostasis in zebrafish are under the control of antagonistic Pomca neurons and Agrp neurons of the arcuate nucleus of the hypothalamus. In this study, we identified hypothalamic Pomca neurons projecting to the main visual processing center of the larval zebrafish brain, the optic tectum. Tectal periventricular neurons (PVNs) showed expression of melanocortin 4 receptor (mc4r), possibly acting as second-order cellular targets of Pomca neurons and modulating sensitivity of the fish to visual food stimuli. We explored the modulatory role of this circuitry by interfering with mc4r globally using pharmacological drugs (Melanotan-II, an α-MSH analogue) and recording calcium responses in tectal PVNs, while presenting visual prey-like stimuli to the fish. We observed that energy state of the animal under the homeostatic control of the melanocortin system could modulate excitability of tectal PVNs. These effects were also translated at the behavioral level in an approach versus avoidance assay. Additionally, tectal-specific disruption of mc4r signaling with a dominant-negative mc4r variant in sated fish increased approach-like hunting behavior similar to a hungry larva. These findings highlight the functional importance of Pomca innervations in the optic tectum of larval zebrafish and the role of melanocortin circuitry in modulating visual processing and decision making during foraging behavior.