Morphological and functional analysis of the neuronal melanocortin circuitry and its modulation of visual processing during feeding behavior

• Applicant: Dominique Förster, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Developmental Neurobiology ; Experimental and Theoretical Network Neuroscience
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544966926

Energy homeostasis, i.e. the coordinated control of food intake and energy expenditure, is critical for health and survival. Feeding behavior is dependent on sensory systems and regulated by several neuromodulatory mechanisms, which are often overlapping and interconnected. Due to comparably high complexity of the brain of common mammalian model systems, the underlying neuromodulatory circuitries and their influence on sensory brain centers are largely unknown. Here, I propose to investigate the role of melanocortin signaling for the processing of visual food stimuli and its influence on foraging behavior, using larval zebrafish as a model system. In this work program, my group will first study the neuronal architecture of the zebrafish central melanocortin system. We will systematically characterize the anatomy, connectivity, and function of two antagonistic cell populations in the hypothalamus: agouti-related peptide (agrp)- and melanocortin (pomc)-expressing neurons, which promote and suppress feeding, respectively. According to preliminary data, axons of these cells target the tectum, the visual processing center in fish, providing a possible link to sensory food detection. We will establish a morphological catalog of both cell types and their axonal target regions in the brain. Second, we will interrogate synaptic connectivity of agrp- and pomc-expressing neurons using our recently published whole-brain electron-microscopic zebrafish dataset. This will allow the identification of upstream and downstream connected partner cells and thus for the first time reveal the connectome of the central melanocortin network in the vertebrate brain. Third, we will investigate the functional role of melanocortin signaling for visual processing and feeding behavior. We will monitor neuronal activity in the tectum and prey capture behavior upon interference with the Agrp/Pomc system. Furthermore, we will morphologically and functionally describe the melanocortin receptor-expressing tectal cells and elucidate their contribution to sensory-motor transformation of food stimuli. Taken together, the results of this proposal will provide detailed insights into the cellular- and circuitry-level mechanisms via which the melanocortin system fulfills its neuromodulatory effects with respect to sensory processing and feeding behavior. These findings will have implications for understanding the biology of metabolic disorders.

• DFG Programme: Research Grants