4.8 Article

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

Journal

SCIENCE ADVANCES
Volume 8, Issue 39, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abo0549

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Funding

  1. Intramural Research Program of the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD)

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Sudden changes in the environment can trigger defensive behavior, such as tonic immobility, in organisms. This study reveals that a strong vibratory stimulus can induce tonic immobility in larval zebrafish through the regulation of cerebellar granule cells and a cluster of glutamatergic ventral prepontine neurons (vPPNs) that express stress-associated neuropeptides.
Sudden changes in the environment are frequently perceived as threats and provoke defensive behavioral states. One such state is tonic immobility, a conserved defensive strategy characterized by powerful suppression of movement and motor reflexes. Tonic immobility has been associated with multiple brainstem regions, but the underlying circuit is unknown. Here, we demonstrate that a strong vibratory stimulus evokes tonic immobility in larval zebrafish defined by suppressed 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 sensory ganglia 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 an inescapable threat.

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