Data from: Norepinephrine signals through astrocytes to modulate synapses

Locus coeruleus (LC)-derived norepinephrine (NE) drives network and
behavioral adaptations to environmental saliencies by reconfiguring
circuit functional connectivity, but the underlying synapse-level
mechanisms are elusive. Here, we show that NE remodeling of synaptic
function is independent from its binding on neuronal receptors. Instead,
astrocytic adrenergic receptors and Ca2+ dynamics fully gate the effect of
NE on synapses as the astrocyte-specific deletion of adrenergic receptors
and three independent astrocyte-silencing approaches all render synapses
insensitive to NE. Additionally, we find that NE suppression of synaptic
strength results from an ATP-derived and adenosine A1 receptor-mediated
control of presynaptic efficacy. An accompanying study from Chen et al.
reveals the existence of an analogous pathway in the larval zebrafish and
highlights its importance to behavioral state transitions. Together, these
findings support a new model wherein astrocytes are a core component of
neuromodulatory systems and the circuit effector through which
norepinephrine produces network and behavioral adaptations.