Multiple Rhythm-Generating Circuits Act in Tandem with Pacemaker Properties to Control the Start and Speed of Locomotion

In vertebrates, specific command centers in the brain can selectively drive slow-explorative or fast-speed locomotion. However, it remains unclear how the locomotor central pattern generator (CPG) processes descending drive into coordinated locomotion. Here, we reveal, in adult zebrafish, a logic of the V2a interneuron rhythm-generating circuits involving recurrent and hierarchical connectivity that acts in tandem with pacemaker properties to provide an ignition and gear-shift mechanism to start locomotion and change speed. A comprehensive mapping of synaptic connections reveals three recurrent circuit modules engaged sequentially to increase locomotor speed. The connectivity between V2a interneurons of different modules displayed a clear asymmetry in favor of connections from faster to slower modules. The interplay between V2a interneuron pacemaker properties and their organized connectivity provides a mechanism for locomotor initiation and speed control. Thus, our results provide mechanistic insights into how the spinal CPG transforms descending drive into locomotion and align its speed with the initial intention. [Display omitted] •V2a interneurons form three recurrent speed-dependent circuit modules•Inter-module V2a connections show a faster-to-slower hierarchy of strength•A subset of V2a interneurons displays intrinsic pacemaker properties•Pacemaker properties and connectivity rules underlie locomotor start and speed Song et al. reveal a unique logic of the locomotor rhythm-generating network in vertebrates. The interplay between pacemaker properties and recurrent and hierarchical connections between V2a interneurons provides an ignition and gear-shift mechanism to start locomotion and change its speed.