A cerebellar-prepontine circuit for tonic immobility triggered by inescapable threat

Abstract

Sudden changes in the sensory environment are frequently perceived as threats and may provoke defensive behavioral states. One such state is tonic immobility, a conserved defensive strategy characterized by a powerful suppression of movement and motor reflexes. Tonic immobility has been associated with multiple brainstem regions and cell types, but the underlying circuit is not known. Here, we demonstrate that a strong vibratory stimulus evokes tonic immobility in larval zebrafish defined by suppression of exploratory locomotion and sensorimotor responses. Using a circuit-breaking screen and targeted neuron ablations, we show that cerebellar granule cells and a cluster of glutamatergic ventral prepontine neurons (vPPNs) that express key stress-associated neuropeptides are critical components of the circuit that suppresses movement. The complete sensorimotor circuit transmits information from primary sensory neurons through the cerebellum to vPPNs to regulate reticulospinal premotor neurons. These results show that cerebellar regulation of a neuropeptide-rich prepontine structure governs a conserved and ancestral defensive behavior that is triggered by inescapable threat.