Noradrenergic Circuit Adaptations Underlying Predatory Aggression

Abstract

Behaviors are adaptive traits shaped by natural selection. Nevertheless, the genetic, molecular, and neural modifications that underlie behavioral innovations remain poorly understood. Here, I identify specialized adaptations linked to the evolution of invertebrate aggression by leveraging a comparative nematode framework, <em>Pristionchus pacificus</em> versus <em>Caenorhabditis elegans</em>, to dissect the evolution of predatory aggression and its interface with territoriality and feeding. We combined high throughput tracking with a semi-supervised behavioral state labeling pipeline, cell type resolved perturbations, receptor mapping, and targeted CRISPR screens. Quantitative analyses revealed that octopamine and tyramine function as an antagonistic pair at the molecular level: <em>tbh-1</em> loss (↓octopamine) reduced entry into the predatory state, <em>tdc-1</em> loss (↓tyramine and ↓octopamine) rescued this effect. Furthermore, exogenous octopamine and tyramine also shifted state occupancy in opposite directions. Behavioral assays of CRISPR mutants showed that mutations in the octopamine receptors <em>ser-3/ser-6</em> phenocopied <em>tbh-1</em> deficits, whereas mutations in the tyramine associated ion channel, <em>lgc-55</em> mirrored the rescue observed in <em>tdc-1</em>. Crucially, we found that while the neurotransmitter source remained conserved across species, the receptor expression has been rewired with differential expression observed across head sensory neurons. Notably, <em>P. pacificus</em> specific SER-3 expression is detected in IL2 sensory neurons and functional silencing of these reduces predatory search, biting, and feeding. This establishes the IL2 neurons as a sensory hub for prey detection and state gating. Comparative tests across another basal Diplogastrid species indicate that octopamine's pro-aggressive role is conserved within this family. Thus adaptations in noradrenergic circuits emerges as a central mechanism for shaping the evolution of aggressive behavioral states in nematodes.