Circuit-constrained molecular neuroethology in the medicinal leech Hirudo verbana

Medicinal leeches have long served as classic systems in comparative neuroethology because individual neurons can be identified across animals and linked to well-defined behaviors. This review argues that Hirudo verbana is now positioned for a new phase in which this identified-cell framework can be connected directly to molecular mechanisms. We first outline the organization and experimental accessibility of the leech nervous system, then evaluate genomic and transcriptomic resources as tools for testing physiologically constrained hypotheses rather than as endpoints in themselves. We focus on selected problems in which behavior, identified neurons, and molecular candidates can be brought into close alignment: sensory encoding, serotonergic state-dependent gating, multifunctional behavioral circuits, heartbeat rhythm generation, and endocannabinoid-dependent plasticity. Across these examples, the comparative value of Hirudo verbana lies not in nervous-system simplicity alone, but in interpretability: receptors, ion channels, pumps, peptides, gap-junction proteins, and metabolic enzymes can be examined in relation to cellular and circuit operations already defined by physiology. Future progress will require tighter integration of circuit-defined phenotypes with cell-resolved transcriptomics, spatial localization, targeted perturbation, and quantitative modeling. This circuit-constrained strategy positions Hirudo verbana as a valuable bridge between classical identified-cell neuroethology and molecular tests of circuit physiology.