Abstract: Whether astrocytes play direct roles in information processing in the brain has remained controversial. Astrocytes associate with synapses throughout the brain and express receptors for neurotransmitters that can, in some cases, elevate intracellular Ca2+. Astrocyte Ca2+ signaling has been proposed to modulate neural circuit activity, but molecular pathways regulating these events are poorly defined and in vivo evidence linking changes in astrocyte Ca2+ to alterations in neurotransmission and/or behavior is limited. This seminar will discuss how astrocytes receive neurotransmitter signals from neurons, process that information via Ca2+ signals and ultimately use that signaling to regulate downstream neuron activity. The primary signaling pathway, which involves neuronal adrenergic signaling to astrocytes followed by astrocytic purinergic signaling to neurons, is highly conserved from Drosophila to mammals and can change flexibly change astrocyte responsiveness to other neurotransmitters with brain state. Our work supports the notion that astrocytes are integral components of neural circuits and actively participate information processing.