A glial source of noradrenaline shapes synaptic integration and motor adaptation

Abstract

Noradrenaline is a major neuromodulator that shapes neural circuit dynamics and behavior. Prevailing models attribute noradrenergic supply exclusively to long-range inputs from distant nuclei. Yet noradrenergic input can be weak in regions that nonetheless show marked noradrenergic modulation, suggesting additional sources. This mismatch is salient in the cerebellum, where noradrenaline influences behavior despite sparse innervation. Here, we identify Bergmann glia, radial cerebellar astrocytes, as a source of noradrenaline. Using two-photon imaging and cell-type-specific genetic manipulations, we show that Bergmann glia can synthesize and release noradrenaline through a calcium-dependent mechanism requiring the vesicular monoamine transporter VMAT2. Glia-derived noradrenaline modulates synaptic integration in Purkinje neurons and is required for motor adaptation. Together, these findings identify a glial pathway that complements the canonical long-range view of noradrenaline supply.