Glial cells are an integral part of functional communication in the brain. Here we show that astrocytes contribute to the fast dynamics of neural circuits that underlie normal cognitive behaviors. In particular, we found that the selective expression of tetanus neurotoxin (TeNT) in astrocytes significantly reduced the duration of carbachol-induced gamma oscillations in hippocampal slices. These data prompted us to develop a novel transgenic mouse model, specifically with inducible tetanus toxin expression in astrocytes. In this in vivo model, we found evidence of a marked decrease in electroencephalographic (EEG) power in the gamma frequency range in awake-behaving mice, whereas neuronal synaptic activity remained intact. The reduction in cortical gamma oscillations was accompanied by impaired behavioral performance in the novel object recognition test, whereas other forms of memory, including working memory and fear conditioning, remained unchanged. These results support a key role for gamma oscillations in recognition memory. Both EEG alterations and behavioral deficits in novel object recognition were reversed by suppression of tetanus toxin expression. These data reveal an unexpected role for astrocytes as essential contributors to information processing and cognitive behavior.glia | electroencephalogram | network oscillation | gliotransmitter | glial fibrillary acidic protein I n the brain, the spatial and temporal coordination of networks of cells underlies both homeostatic and cognitive functions. Such synchronous activity gives rise to fluctuating local field potentials that can be recorded on the surface of the scalp by electroencephalography (EEG). Fast local field potential oscillations in the gamma frequency band (γ 25-80 Hz) have been closely correlated with learning, memory storage and retrieval, attention, and other cognitive or motor functions (1). In addition, in several neuropsychiatric disorders, gamma oscillations exhibit significant abnormalities that often correlate with the severity of the symptoms: a reduction in gamma oscillations is characteristic of the negative symptoms of schizophrenia, Alzheimer's disease, and autism, whereas the positive symptoms of schizophrenia, epilepsy, and attention-deficit hyperactivity disorder show increased gamma amplitudes (2). Nonetheless, the molecular mechanisms underlying these oscillations are poorly understood. Although the inhibitory interneurons (3, 4) and neuronal gap junction proteins 6) have all been shown to contribute to gamma oscillations, many of the molecular, cellular, and network mechanistic details underlying oscillations still remain undefined. Furthermore, the role of oscillations in brain function and behavior has yet to be fully clarified.In the present work, we have moved away from the traditional focus of network oscillation research, namely neurons, and have instead investigated the consequences of a functional manipulation of astrocytes on network function and animal behavior. The role of astrocytes in maintaining the brain's en...

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