A two-layer neural circuit controls fast forward locomotion in Drosophila

Fast forward locomotion is critical for animal hunting and escaping behaviors. However, how the underlying neural circuit is wired at synaptic resolution to decide locomotion direction and speed remains poorly understood. Here, we identified in the ventral nerve cord (VNC) a set of ascending cholinergic neurons (AcNs) to be command neurons capable of initiating fast forward peristaltic locomotion in Drosophila larvae. Targeted manipulations revealed that AcNs are necessary and sufficient for fast forward locomotion. AcNs can activate their postsynaptic partners, A01j and A02j; both are interneurons with locomotory rhythmicity. Activated A01j neurons form a posterior-anteriorly descendent gradient in output activity along the VNC to launch forward locomotion from the tail. Activated A02j neurons exhibit quicker intersegmental transmission in activity that enables fast propagation of motor waves. Our work revealed a global neural mechanism that coordinately controls the launch direction and propagation speed of Drosophila locomotion, furthering the understanding of the strategy for locomotion control.