Dallmann, C.J., Luo, Y., Agrawal, S., Mamiya, A., Chou, G.M., Cook, A., Sustar, A., Brunton, B.W., Tuthill, J.C. (2025). Selective presynaptic inhibition of leg proprioception in behaving Drosophila.  Nature 647(8089): 445--453.

FBrf0263858

Research paper

Controlling arms and legs requires feedback from the proprioceptive sensory neurons that detect joint position and movement[1,2]. Proprioceptive feedback must be tuned for different behavioural contexts[3-6], but the underlying circuit mechanisms remain poorly understood. Here, using calcium imaging in behaving Drosophila, we find that the axons of position-encoding leg proprioceptors are active across a range of behaviours, whereas the axons of movement-encoding leg proprioceptors are suppressed during walking and grooming. Using connectomics[7-9], we identify a specific class of interneurons that provide GABAergic presynaptic inhibition to the axons of movement-encoding proprioceptors. These interneurons receive input from parallel excitatory and inhibitory descending pathways that are positioned to drive the interneurons in a context-specific and leg-specific manner. Calcium imaging from both the interneurons and their descending inputs confirms that their activity is correlated with self-generated but not passive leg movements. Taken together, our findings reveal a neural circuit that suppresses specific proprioceptive feedback signals during self-generated movements.