The synchronization of neuronal assemblies during cortical UP states has been implicated in computational and homeostatic processes, but the mechanisms by which this occurs remain unknown. To investigate potential roles of astrocytes in synchronizing cortical circuits, we electrically activated astrocytes while monitoring the activity of the surrounding network with electrophysiological recordings and calcium imaging. Stimulating a single astrocyte activates other astrocytes in the local circuit and can trigger UP state synchronizations of neighboring neurons. Moreover, interfering with astrocytic activity with intracellular injections of a calcium chelator into individual astrocytes inhibits spontaneous and stimulated UP states. Finally, both astrocytic activity and neuronal UP states are regulated by purinergic signaling in the circuit. These results demonstrate that astroglia can play a causal role in regulating the synchronized activation of neuronal ensembles.T he transient synchrony of distributed groups of neurons is an important operational characteristic of the cerebral cortex for sensory processing and internal computational functions (1-4). One important type of synchrony-the multineuronal, network-driven fluctuations in membrane potential known as UP and DOWN states-occurs in neocortex both in vitro and in vivo (5-11). During UP states, neurons are depolarized for up to hundreds of milliseconds, sometimes firing barrages of action potentials (12). The function of these UP states is unknown, although they underlie synchronization among distant cortical territories (13). UP states in vivo are observed at similar frequencies as the "resting" spontaneous activity that is evident in functional MRI and EEG recordings from human subjects when not involved in sensory motor tasks (14-16), so they may be a cellular basis of this activity.The mechanisms by which UP states occur remain unclear, although recurrent excitatory activity is important (6, 9). Because astrocytes regulate extracellular glutamate (17), we explored their effects on cortical UP states using electrophysiology and population calcium imaging. The effects of astroglia on synaptic transmission and plasticity have been intensely studied, but their role in coherent function of the circuit has received much less attention, even though glia constitute almost half of all of the cells in the adult human brain (17) and are well-suited for longrange, network-wide signaling. Astrocytes also tile the cortex with near-complete coverage (18,19), are connected into an extensive syncytium via gap junctions (20,21), and communicate by intercellular calcium signaling (22), and processes from a single astrocyte can contact up to tens of thousands of synapses (18), making them attractive candidates for mediating neuronal synchronization. Here we describe a role of astrocytes in the cortical circuit, demonstrating their importance in the modulation of neuronal UP states.Results UP States Are Network-Wide Events. We performed whole-cell patch clamping of neurons i...