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.
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.
|Gaine, Marie E; Chatterjee, Snehajyoti; Abel, Ted (2018) Sleep Deprivation and the Epigenome. Front Neural Circuits 12:14|
|Günther, Anne; Luczak, Vince; Abel, Ted et al. (2017) Caspase-3 and GFAP as early markers for apoptosis and astrogliosis in shRNA-induced hippocampal cytotoxicity. J Exp Biol 220:1400-1404|
|Havekes, Robbert; Abel, Ted (2017) The tired hippocampus: the molecular impact of sleep deprivation on hippocampal function. Curr Opin Neurobiol 44:13-19|
|Qi, Guanxiao; van Aerde, Karlijn; Abel, Ted et al. (2017) Adenosine Differentially Modulates Synaptic Transmission of Excitatory and Inhibitory Microcircuits in Layer 4 of Rat Barrel Cortex. Cereb Cortex 27:4411-4422|
|Gerstner, Jason R; Perron, Isaac J; Riedy, Samantha M et al. (2017) Normal sleep requires the astrocyte brain-type fatty acid binding protein FABP7. Sci Adv 3:e1602663|
|Gerstner, Jason R; Koberstein, John N; Watson, Adam J et al. (2016) Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex. BMC Genomics 17:727|
|Watson, Adam J; Henson, Kyle; Dorsey, Susan G et al. (2015) The truncated TrkB receptor influences mammalian sleep. Am J Physiol Regul Integr Comp Physiol 308:R199-207|
|Vecsey, Christopher G; Park, Alan J; Khatib, Nora et al. (2015) Effects of sleep deprivation and aging on long-term and remote memory in mice. Learn Mem 22:197-202|
|Frank, Marcos G (2013) Astroglial regulation of sleep homeostasis. Curr Opin Neurobiol 23:812-8|
|Watson, Adam J; Frank, Marcos G (2013) Astrocytes do the ""shuttle"". Sleep 36:1413-4|