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Non-neuronal regulators of sleep

$453,081R01FY2014MHNIH

Washington State University, Pullman WA

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): Sleep problems such as excessive daytime sleepiness and insomnia are common in the United States. They are found in many psychiatric and neurological disorders and cause deficits in attention, learning and memory. The cellular mechanism that makes animals sleepy and causes cognitive deficits in sleepy animals is unknown. Chemical signaling between glia and neurons (i.e. gliotransmission) may be an important part of this mechanism. Glial astrocytes are brain cells that are electrically silent (relative to neurons) and for many decades were thought to serve purely supportive functions in the brain (e.g. ion buffering). More recent findings indicate that astrocytes are important partner in synaptic neurotransmission. Astrocytes surround synapses and respond to neurotransmitters by secreting their own chemical messengers (gliotransmitters), which in turn regulate neuronal excitability and synaptic transmission. The role of gliotransmission in mammalian behavior is only now beginning to be explored. In mammals astrocytes are densely concentrated in brain regions critical for arousal, sleep and higher cognitive function. We hypothesize that gliotransmission in these regions mediates not only sleepiness, but cognitive deficits associated with sleep loss. We will test our hypothesis by quantitatively measuring sleep regulation in mice with an inducible (conditional) mutation that inhibits astrocytic gliotransmission in vivo. We will also use these mice test the role of gliotransmission in learning and attention deficits caused by sleep loss. Our findings will thus provide new insights into the cellular basis of sleep need and the function of non- neuronal cells in animal behavior.

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