Boivin, J.-C. | bioRxiv Science

bioRxiv2025

A positive feedback loop between sensory and octopaminergic neurons underlies nociceptive plasticity in Drosophila larvae

Adaptive modulation of nociceptive behaviour based on prior experience is essential for responding effectively to environmental threats. In Drosophila larvae, nociceptive escape behaviours are robust and stereotyped, yet emerging evidence suggests this can be modulated by experience and internal state. Here, we demonstrate that repeated activation of nociceptive sensory neurons enhances both the likelihood and intensity of nocifensive rolling, reflecting a form of behavioural sensitization. This heightened responsiveness is accompanied by a sustained increase in activity within nociceptive sensory neurons, suggesting that plasticity arises, at least in part, within the sensory compartment. We identified the neuromodulator octopamine as a critical regulator of the sensitization: signalling through the octopamine receptor OAMB is required to sustain elevated nociceptive gain, and feedback from one of octopaminergic neurons class, the ventral unpaired median (VUM) neurons, amplifies sensory neuron output. Together, these findings reveal an experience-dependent positive feedback loop in the nociceptive system, where neuromodulatory circuits tune behavioural output.

neuroscience↗

bioRxiv2023

Feedback inhibition by a descending GABAergic neuron regulates timing of escape behavior in Drosophila larvae

Escape behaviors help animals avoid harm from predators and other threats in the environment. Successful escape relies on integrating information from multiple stimulus modalities (of external or internal origin) to compute trajectories toward safe locations, choose between actions that satisfy competing motivations, and execute other strategies that ensure survival. To this end, escape behaviors must be adaptive. When a Drosophila melanogaster larva encounters a noxious stimulus, such as the focal pressure a parasitic wasp applies to the larval cuticle via its ovipositor, it initiates a characteristic escape response. The escape sequence consists of an initial abrupt bending, a corkscrew-like rolling, and finally rapid crawling. Previous work has shown that the detection of noxious stimuli primarily relies on class IV multi dendritic arborization neurons (Class IV neurons) located beneath the body wall, and more recent studies have identified several important components in the nociceptive neural circuitry involved in rolling. However, the neural mechanisms that underlie the rolling-escape sequence remain unclear. Here we present both functional and anatomical evidence suggesting that bilateral descending neurons within the subesophageal zone of D. melanogaster larva play a crucial role in regulating the termination of rolling and subsequent transition to escape crawling. We demonstrate that these descending neurons (designated SeIN128) are inhibitory and receive inputs from a second-order interneuron upstream (Basin-2) and an ascending neuron downstream of Basin-2 (A00c). Together with optogenetic experiments showing that co-activation of SeIN128 neurons and Basin-2 influence the temporal dynamics of rolling, our findings collectively suggest that the ensemble of SeIN128, Basin-2, and A00c neurons forms a GABAergic feedback loop onto Basin-2, which inhibits rolling and thereby facilitates the shift to escape crawling.

neuroscience↗