Noradrenaline prolongs the state of motor arrest via cerebrospinal fluid signaling

Abstract

Neuromodulators can mediate whole-body physiological changes, however how signaling from relatively small populations of neurons produces widespread and sustained effects remains incompletely understood. Here, we demonstrate that sustained noradrenergic activation induces prolonged motor arrest accompanied by postural collapse, bradycardia, and emetic responses. Motor suppression arises from inhibition of brainstem commands to the spinal cord rather than motoneuron silencing. Noradrenaline induces a glial calcium wave that propagates throughout the central nervous system. This wave most prominently persists at the brainstem-spinal cord boundary and ventricular midline. At this location, ependymal radial glia express Adra1a receptors on cilia contacting cerebrospinal fluid (CSF). Ventricular noradrenaline injections recapitulated the glial wave and motor arrest, while CSF administration of an Adra1 antagonist shortened motor arrest. Altogether, noradrenaline sustains motor arrest by signaling through the CSF via ciliary Adra1a receptors on ependymal radial glia showing that cerebrospinal fluid as a critical transmission route for persistence of behavioral states. HighlightsO_LINoradrenergic surges coordinate a whole-body response with motor arrest, postural disruptions, bradycardia, and emesis-like reflexes C_LIO_LIMotor arrest results from silencing of brainstem motor commands to the spinal cord C_LIO_LINoradrenaline-induced glial calcium waves last longest at the obex/ventricular midline where cilia of CSF-contacting glial cells bear Adra1 receptors C_LIO_LINoradrenergic signaling in the CSF is necessary and sufficient for motor arrest to persist C_LI