The role of astrocytes in neuronal function has received increasing recognition, but disagreement remains about their function at the circuit level. Here we use in vivo two-photon calcium imaging of neocortical astrocytes while monitoring the activity state of the local neuronal circuit electrophysiologically and optically. We find that astrocytic calcium activity precedes spontaneous circuit shifts to the slow-oscillation-dominated state, a neocortical rhythm characterized by synchronized neuronal firing and important for sleep and memory. Further, we show that optogenetic activation of astrocytes switches the local neuronal circuit to this slow-oscillation state. Finally, using two-photon imaging of extracellular glutamate, we find that astrocytic transients in glutamate co-occur with shifts to the synchronized state and that optogenetically activated astrocytes can generate these glutamate transients. We conclude that astrocytes can indeed trigger the low-frequency state of a cortical circuit by altering extracellular glutamate, and therefore play a causal role in the control of cortical synchronizations.he neocortical slow oscillation (∼1 Hz) that defines slowwave sleep (SWS) is believed to play a critical role in memory consolidation by coordinating cell assemblies in areas within and outside the cortex (1-4). This cortical state is in marked contrast to rapid-eye-movement (REM) sleep and wakefulness, which are dominated by low-amplitude and high-frequency cortical activity (5). Slow cortical rhythms are also observed during the waking state, as well as during sleep (6-10), suggesting widespread functional roles for this oscillation. Although the slow oscillation is cortically generated (11)(12)(13)(14), the circuit mechanisms that drive the cortex into the slow-wave state remain unclear. Because neuronal responses to external stimuli are modulated by brain state, the mechanisms that drive transitions to different states-the relatively synchronized, slow-oscillation-dominated state or the desynchronized, more "awake" or attentive state-have recently been of intense interest, although most of these have focused on the shift to the desynchronized state (15)(16)(17)(18)(19). These studies have critically examined the effects of neuronal and sensory manipulations on brain state and the effects of brain state on processing, but have not investigated how other cellular circuit components may influence these states.Astrocytes have been implicated in SWS and the regulation of UP states-the cellular underpinnings of the slow oscillation (20-23)-and are attractive candidates for carrying out a widespread circuit role because each astrocyte has the potential to influence thousands of synapses simultaneously (24). However, the methodology used to demonstrate an astrocyte-specific function in regulation of SWS (21) and the slow oscillation (22) has become controversial (25, 26), leaving astrocytes' role in the generation of the slow-oscillation state uncertain. In addition, there are few data on astrocytes' roles in acu...