MAPPING A COMPLETE CIRCUIT UNDERLYING FLEXIBLE SENSORIMOTOR TRANSFORMATIONS

Flexible sensorimotor behaviors are crucial for survival, and their disruption can lead to neurological and movement disorders. However, how neural circuits flexibly select and execute context-appropriate motor actions remains unclear. The Drosophila larva, with its genetic accessibility and complete synaptic connectome, offers a powerful system for studying these mechanisms. Building on our previous work identifying neural circuits in the ventral nerve cord (VNC) that underlie competitive selection between startle-type and escape actions (Jovanic et al., 2016; Lehman et al., 2025), we have been investigating how this information is conveyed to motor circuits to generate specific motor outputs and to map ascending and descending pathways linking sensorimotor circuits in the VNC to the brain. Using functional imaging and the electron microscopy (EM) connectome, we identified the muscles, their corresponding motor neurons, and putative premotor neurons involved in a startle behavior. We further connected them to upstream sensory circuits. We also identified two thoracic descending neurons that promote or inhibit the startle behavior and two ascending neurons that suppress it. EM connectivity analysis revealed that the ascending neurons indirectly target neuropeptidergic brain neurons, which in turn provide input to the descending neurons, forming a functional link between the higher-order brain regions and VNC circuits. These results lay the foundation for functionally mapping a complete sensorimotor circuit across the nervous system and understanding how these pathways coordinate context-dependent motor outputs. This work in Drosophila larvae will advance our understanding of circuit principles underlying context-appropriate sensorimotor transformations applicable to more complex brains.