Astrocytes amplify neuronal dendritic volume transmission

Abstract

In addition to their support role in neurotransmitter and ion buffering, astrocytes directly regulate neurotransmission at synapses via local bidirectional signaling with neurons. Here, we reveal a new form of neuronal-astrocytic signaling that transmits retrograde dendritic signals to upstream neurons to activate recurrent synaptic circuits. Norepinephrine activates 1-adrenoreceptors in hypothalamic corticotropin releasing factor (CRF) neurons to stimulate dendritic release, which triggers an astrocytic calcium response and release of ATP; ATP stimulates action potentials in upstream glutamate and GABA neurons to activate recurrent excitatory and inhibitory synaptic circuits to the CRF neurons. Thus, norepinephrine activates a novel retrograde signaling mechanism in CRF neurons that engages astrocytes in order to extend dendritic volume transmission to reach distal presynaptic glutamate and GABA neurons, thereby amplifying volume transmission mediated by dendritic release.