Molecular, functional, and behavioral analysis of neuromodulatory networks in the zebrafish telencephalon

In all metazoans, neural circuit function is subject to regulation by state-specific neuromodulation. Here, we mapped the expression of neuromodulatory systems in the zebrafish telencephalon to ultimately understand their contributions to memory formation. We first generated a comprehensive single-cell RNA sequencing dataset of the telencephalon of adult zebrafish and mapped the diversity of neuronal cell types to anatomical brain areas. Gene expression data of G-protein coupled receptors were mined to embed individual cell types in neuromodulatory networks, allowing inference about which modulators influence each brain area and cell type. Ultimately, we provide evidence that several cell populations and areas are evolutionarily conserved between fish and lizards, such as a potential homologue of the hippocampal formation. This dataset is now being combined with a functional imaging approach that measures neuronal population activity during behavior. To this aim, 2-photon calcium imaging in the telencephalon of adult zebrafish is performed in a virtual reality and the formation of neuronal representations in the dorsal pallium during spatial learning is analyzed. This work exploits the link between gene expression and activity data, enabling further investigation of the possibility that multiple neuromodulatory systems act in combination during cognitive tasks and synergistically contribute to network functionality during memory formation.