MAPPING OF ACTION SELECTION CIRCUITS FROM SENSORY INPUT TO DESCENDING NEURONS

To survive and reproduce, animals seek rewarding stimuli while avoiding aversive cues and potential threats. Although sensory encoding, feature extraction, and decision-making have been extensively studied across species, the downstream neural pathways that translate sensory information into specific actions remain poorly understood.
Here, we systematically screened action-selection circuits in Drosophila larvae using large-scale optogenetic screening. We identified 58 split-GAL4 lines in which activation of individual neurons elicited distinct locomotor behaviors, including forward crawling, turning or casting, backward crawling, hunching, and rolling. Notably, most neurons bidirectionally regulated behavior, such that activation and inhibition drove opposing actions.
By integrating neuronal morphology derived from connectomic datasets with light-microscopy images of transgenically labelled neurons in split-GAL4 lines, we reconstructed complete circuits linking sensory neurons to descending motor pathways across multiple neuronal layers. Using optogenetics and calcium imaging, we further characterized the sensory response profiles of these neurons. Crawl-promoting neurons were activated by appetitive stimuli and suppressed by aversive stimuli, whereas turning- and backward-crawling–promoting neurons responded selectively to aversive inputs.
Together, our findings reveal circuit-level principles by which sensory valence is transformed into appropriate motor actions, providing a comprehensive framework for understanding action selection downstream of sensory processing.