Synaptic connectome of a neurosecretory network in the Drosophila brain

Abstract

Hormones mediate inter-organ signaling, which is crucial in orchestrating diverse behaviors and physiological processes, including sleep and activity, feeding, growth, metabolism, and reproduction. The pars intercerebralis and pars lateralis in insects represent major hubs that contain neurosecretory cells (NSCs) that produce various peptide hormones. To obtain insight into how hormonal signaling is regulated, we have characterized the synaptic connectome of NSCs in the adult Drosophila brain. Identification of neurons providing inputs to multiple NSC classes implicates diuretic hormone 44-expressing NSCs as a major coordinator of physiology and behavior. Surprisingly, despite most NSCs having dendrites in the subesophageal zone (primary taste processing center), inputs from peripheral gustatory neurons to NSCs are largely indirect. We also deciphered pathways via which diverse olfactory inputs are relayed to NSCs. Using an influence metric, based on a linear dynamical systems approach, we identify enteric neurons as the strongest influencers of NSC activity compared to other sensory modalities. Further, our analyses revealed substantial inputs from brain descending neurons to NSCs, suggesting that descending neurons regulate both endocrine and motor output to synchronize physiological changes with appropriate behaviors. In contrast to NSC inputs, synaptic output from NSCs is sparse and mostly mediated by corazonin NSCs. We show that both corazonin-expressing NSCs and their downstream synaptic partner DNg27 influence egg-laying. We additionally explore putative paracrine interconnectivity between NSC classes and peptide hormone pathways from NSCs to peripheral tissues by analyzing single-cell transcriptomic datasets. Our comprehensive characterization of the Drosophila neurosecretory network connectome provides a platform to understand complex hormonal networks and how they orchestrate animal behaviors and physiology.