Connectome simulations identify a central pattern generator circuit for fly walking

Area of Science:

• Neuroscience
• Animal Locomotion
• Computational Biology

Background:

• Animal locomotion is controlled by central pattern generators (CPGs), neural circuits producing rhythmic output.
• The specific cellular structure of a walking CPG remains unknown across all animal species.

Purpose of the Study:

• To identify the specific neurons and synaptic connections forming the CPG for walking in *Drosophila*.
• To elucidate the neural basis of rhythmic leg movements in flies.

Main Methods:

• Dynamic simulations of *Drosophila* ventral nerve cord (VNC) connectomes.
• Computational activation screening of descending neurons.
• Network pruning simulations to isolate minimal circuits.
• Experimental validation using optogenetics in behaving flies.

Main Results:

• The descending neuron DNg100 was identified as a key driver of rhythmic leg motor activity.
• A minimal three-neuron circuit (one inhibitory, two excitatory interneurons) was found to be necessary and sufficient for generating six-leg rhythmic motor output.
• A separate descending pathway, DNb08, was predicted to drive rhythmic leg movements and experimentally confirmed.

Conclusions:

• The study reveals the cellular identity and synaptic organization of a putative CPG circuit for walking in flies.
• This research provides a foundational understanding of the neural mechanisms underlying rhythmic locomotion.