A specialized spinal circuit for command amplification and directionality during escape behavior

Significance We are constantly faced with a choice moving to the left or right; understanding how the brain solves the selection of action direction is of tremendous interest both from biological and clinical perspectives. In vertebrates, action selection is often considered to be the realm of higher cognitive processing. However, by combining electrophysiology, serial block-face electron microscopy, and behavioral analyses in zebrafish, we have revealed a pivotal role, as well as the full functional connectome of a specialized spinal circuit relying on strong axo-axonic synaptic connections. This includes identifying a class of cholinergic V2a interneurons and establishing that they act as a segmentally repeating hub that receives and amplifies escape commands from the brain to ensure the appropriate escape directionality.