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 willalso 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.

Public Health Relevance

Sleep disorders are associated with cognitive dysfunction; mood disorders and mental illness. Some sleep problems may be caused by abnormalities in 'sleep homeostasis; a process that increases the need for sleep. The cellular mechanisms governing sleep homeostasis are unknown; but may involve non-neuronal brain cells. Identifying the role of these cells in sleep will provide new insights into the cellular basis of sleep and maylead to new classes of drugs for the treatment of sleep disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
7R01MH099544-03
Application #
9000829
Study Section
Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
Program Officer
Vicentic, Aleksandra
Project Start
2013-08-01
Project End
2018-07-31
Budget Start
2014-11-01
Budget End
2015-07-31
Support Year
3
Fiscal Year
2014
Total Cost
$453,081
Indirect Cost
$31,176
Name
Washington State University
Department
Type
Schools of Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
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