Nicotine-driven hyperactivation of larval locomotion

Abstract Balance between excitatory and inhibitory activity is essential for nervous system function. Neuroactive substances like nicotine can disrupt this balance and hyperactivate dopaminergic circuits, with combined effects on behavior and neural activity. We use Drosophila larvae to examine nicotine-induced, linked behavioral changes over multiple time scales by integrating high-resolution locomotor analysis with genetic and pharmacological manipulations. Acute nicotine exposure produces concentration-dependent hyperactivity. Manipulations of the dopaminergic system establish dopamine as the main mediator for motor responses, and further exploration establishes the γ lobe of the mushroom body as a key site for nicotine integration. Experiments with long-term and repetitive nicotine exposure suggest sustained circuit excitability. Finally, nicotine exposure history induces nicotine preference, highlighting experience-dependent plasticity contributing to addiction-like behaviors. These results help establish Drosophila larvae as a model organism to elucidate how neuroactive substances reconfigure neural circuits and behavior. Competing Interest Statement The authors have declared no competing interest.