Molecular logic of neuromodulatory systems in the zebrafish telencephalon

The function of neuronal networks is determined not only by synaptic connectivity but also by neuromodulatory systems that broadcast information via distributed connections and volume transmission. To understand the molecular constraints that organize neuromodulatory signaling in the telencephalon of adult zebrafish we used transcriptomics and additional approaches to delineate cell types, to determine their phylogenetic conservation, and to map the expression of marker genes at high granularity. The combinatorial expression of GPCRs and cell type markers indicates that all neuronal cell types are subject to modulation by multiple monoaminergic systems and distinct combinations of neuropeptides. Individual cell types were associated with multiple (typically >30) neuromodulatory signaling networks but expressed only a few diagnostic GPCRs at high levels, suggesting that different neuromodulatory systems act in combination albeit with unequal weights. These results provide a detailed map of cell types and brain areas in the zebrafish telencephalon, identify core components of neuromodulatory networks, highlight the cell type-specificity of neuropeptides and GPCRs, and begin to decipher the logic of combinatorial neuromodulation.