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Abstract
Astrocytes are known to release several transmitters to impact neuronal activity.
Cell-specific molecular genetic attenuation of vesicular release has shown that ATP
is a primary astrocytic transmitter in situ and in vivo. In this review, we discuss
the biology of astrocytic ATP release highlighting the exciting discovery that lysosomes
might be primary stores for the release of this gliotransmitter. In addition, we discuss
the role of ATP and its metabolite adenosine on synaptic transmission and the coordination
of synaptic networks. Finally, we discuss the recent elucidation of the involvement
of this form of glial signaling in the modulation of mammalian behavior. By controlling
neuronal A1-receptor signaling, astrocytes modulate mammalian sleep homeostasis and
are essential for mediating the cognitive consequences of sleep deprivation. These
discoveries begin to paint a new picture of brain function in which slow-signaling
glia modulate fast synaptic transmission and neuronal firing to impact behavioral
output. Because these cells have privileged access to synapses, they may be valuable
targets for the development of novel therapies for many neurological and psychiatric
conditions.