"The research area of this proposal is Life Science at the intersection of neuroscience, pharmacology and physiology. In the central nervous system (CNS), astrocytes are both numerous and complex. They contact most other cell types in the CNS, and the processes of a single astrocyte can envelop as many as 140,000 synapses. Thus, these cells are uniquely able to receive signals from many sources, in particular synapses, via their G protein-coupled receptors (GPCRs). Additionally, using conventional pharmacological approaches, it has suggested that astrocytes can also send signals to neurons by release of various transmitters to modulate synaptic transmission and plasticity. This reciprocal signaling between neurons and astrocytes (gliotransmission) is still a novel concept, and its physiological relevance remains controversial in the field. In the first part of this proposal, we propose to use novel pharmacogenetic tools that will allow us to selectively activate astrocytes vs. neurons in a more physiological manner to further test the concept of gliotransmission and its role in sleep and memory in vivo. In the second part of this proposal, we will take advantage of these powerful pharmacogenetic tools to test a hypothesis that has heretofore been inaccessible to experimentation, i.e., the possibility that astrocyte GPCRs control glycogen metabolism to modulate synaptic transmission, plasticity, sleep and memory formation. Addressing successfully such major questions in the field of neuroscience, and in particular, resolving some controversies about gliotransmission has profound implications in our understanding of the brain, but also and importantly ,in the clinic. From these studies, we are likely to resolve important aspects of astrocyte function and open up entirely new areas of investigation; this work may lead to potential treatments of diseases, including Alzheimer disease and memory and sleep disorders."