information processing in the brain. We recently (Ripoll-Sanchez et al., 2023) described the first analysis of a wireless neuropeptide connectome using the nematode C. elegans , generating the first comprehensive map of neuropeptide signaling in any animal and describing its structure and topolgy.
We are now using these maps to understand the functional roles of neuropeptide signaling in feeding behaviour. The feeding circuits of C. elegans express peptides and receptors homologous to human hypothalamic peptides that control human appetite and are targeted by anti-obesity drugs. We will use the powerful genetic and optogenetic tools of C. elegans to understand how these peptides control feeding at the circuit and single-neuron level, and explore how their expression is regulated by feeding and starvation.
We would also like to understand how neuropeptide signaling networks are organised in larger brains. For this work, we will focus on the complex yet "alien" brain of the octopus. We have identified >100 putative neuropeptide genes in the octopus genome, some homologous to those in humans, but most with unknown functions. We will identify the receptors for these peptides, map their expression in the octopus hatchling brain, and use electrophysiology and calcium imaging to determine their effects on neural circuits and behaviour.
Funding Notes
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References
Ferguson L, Ouellet S, Vandewyer E, Wang C, Wunna Z, Lim TKY, Schafer WR, Beets I (2026) "DeorphaNN: Virtual screening of GPCR peptide agonists using AlphaFold-predicted active state complexes and deep learning embeddings" Mol Cell 42:113058.
Courtney A, Styfhals R, Van Dijck M, Boulanger J, Geenen L, Lanoizelet M, Hardege I, Lassnig M, Jansson AM, Gehler-Rahman J, Almansa E, Obenhaus H, Seuntjens E, Schafer WR (2025) "Novel dopaminergic neurotransmission in the Octopus visual system" bioRxiv 2025.03.19.644234
Ripoll-Sánchez L, Watteyne J, Sun H, Fernandez R, Taylor SR, Weinreb A, Bentley B, Hammarlund M, Miller DM III, Hobert O, Beets I, Vértes PE, Schafer WR (2023) "The neuropeptidergic connectome of C. elegans" Neuron 111: 3570–3589.
