The human brain contains more than 100 billion cells, the majority being non-excitable glial cells, remarkably coordinated by an intrinsic clock that produce a circadian rhythm in their physiology and behavior. Circadian alterations affect human performances, productivity and are associated to increased risk of human-error related accidents and to a variety of brain disorders (e.g. sleep disorders). However, neuropharmacological R&D faces the lack of knowledge on how this clock signaling is hierarchically orchestrated within so many brain cells to lead to the cycle-to-cycle precision of circadian rhythmicity.Recent studies suggest that astrocytes (the most abundant cells of the brain) actively participate in the modulation of physiological and circadian behavioral processes in invertebrates. Although astrocytes are directly involved in the regulation of synaptic neuronal signaling (“tripartite synapse”), the role of astrocytes in controlling circadian behavior in mammals is largely unknown.This projects converges an original multidisciplinary research program, spanning the fields of molecular neurobiology, neuroelectronics and circadian biology, to unravel the molecular and functional mechanisms by which neurons and astrocytes cooperate to influence circadian rhythmicity in mammals. To do so, innovative genetics, molecular profiling (deep sequencing), behavioral, imaging and electrophysiological approaches will be used. The results of this proposal will lead to a deeper understanding on circadian rhythms in the brain and to the potential identification of new cellular and signaling targets for neuropharmacology.