Astroglia-Neuron Regulation of Sleep
Astroglia-Neuron Regulation of Sleep
批准号:
9189564
负责人:
Priyattam J. Shiromani
金额:
$22.43万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-08-01 至 2018-07-31
关键词:
AccelerometerAction PotentialsAdenosineAdenosine A1 ReceptorAreaArousalAstrocytesBehaviorBrainBrain regionBreathingCellsChemicalsComplexCorpus striatum structureCytoskeletal ProteinsDendritesDevelopmentDrug Delivery SystemsElectrophysiology (science)Genetic EngineeringGlial Fibrillary Acidic ProteinGlutamatesGrantHomeostasisHumanIn VitroLeadLinkMeasuresMediatingMicrodialysisModelingMusNeurogliaNeuronsNeurosciencesPharmacologyPhasePlasmidsPontine structurePosterior HypothalamusProteinsREM SleepRecording of previous eventsRegulationReporter GenesRoleSiteSleepSliceSourceSpecificitySynapsesSynaptic TransmissionTestingTimeWakefulnessWaxesbasal forebrainbasechemical releasecytokineextracellularfeedingin vivonetwork modelsneurotransmissionnew technologyoptogeneticsparticlepromoterresponsesleep regulationsynaptic functiontool
中文摘要
当前的睡眠-觉醒调节模型是“以神经元为中心”的。然而,也有
英文摘要
Current models of sleep-wake regulation are “neuron-centric”. However, there are
astrocytes in the brain, and they outnumber neurons. A single astrocyte contacts hundreds of
dendrites, and tens of thousands of synapses (Bushong et al., 2002, Halassa et al., 2007). The
concept of a tripartite synapse has emerged where astrocytes actively control neuronal activity
and synaptic transmission. We provided the first evidence that selectively activating astrocytes
in the posterior hypothalamus increases both NREM and REM sleep in mice. This is the first
time that optogenetic or DREDD activation of cells other than neurons has been shown to
increase sleep. Most importantly, sleep was increased at night, the normal wake period in
nocturnal mice. This indicates that astrocytes can impart a load that can induce sleep. What
this means is that astrocytes can impart a load on neurons throughout the brain, thus providing
for the first time an explanation for the waxing and waning of sleep. This will support the
hypothesis of “local use dependent sleep” throughout the brain. We will determine the
gliotransmitter that is released, and also monitor the activity of adjacent sleep-wake neurons in
response to optogenetic stimulation. Aim 1 will use microdialysis to test the hypothesis that
adenosine accumulates in response to optogenetic stimulation of ChR2-positive astroglia. We
are focusing on adenosine based on the substantial evidence that it is released from astrocytes
and its linkage with sleep. However, the other potential gliotransmitters will also be measured.
This aim will also use the adenosine A1 receptor antagonist, CPT, to block the sleep induced by
optogenetic stimulation of astrocytes. Aim 2 will test the hypothesis that in response to
optogenetic stimulation of ChR2-positive astroglia the arousal neurons in the posterior
hypothalamus are inhibited, and this is blocked by the adenosine A1 receptor antagonist. This
aim will also determine the site-specificity of the effect in mice by activating the ChR2-containing
astrocytes in areas implicated in sleep-wake regulation (VLPO, basal forebrain, and dorsolateral
pons). The overall impact of this project is that it mechanistically connects astrocytes,
adenosine, A1 receptor, and local neuronal activity with sleep. Inclusion of astrocytes in circuit
models will lead to better explanation of sleep homeostasis, which is something that current
“neuron-centric” models have failed to do.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Neuronal Activity in Sleep & Wake in Alzheimer's Disease Mice
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批准号:10723302
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项目类别:
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资助金额:$15.75万
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财政年份:2023
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负责人:Priyattam J. Shiromani
-
依托单位:
ShEEP Request for iNSCOPIX nVue System
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批准号:10534510
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项目类别:
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资助金额:$0.0万
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财政年份:2022
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负责人:Priyattam J. Shiromani
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依托单位:
BLR&D Research Career Scientist Award Application
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批准号:10618287
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项目类别:
-
资助金额:$0.0万
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财政年份:2018
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负责人:Priyattam J. Shiromani
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依托单位:
BLR&D Research Career Scientist Award Application
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批准号:10454221
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项目类别:
-
资助金额:$0.0万
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财政年份:2018
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负责人:Priyattam J. Shiromani
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依托单位:
BLR&D Research Career Scientist Award Application
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批准号:10265393
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项目类别:
-
资助金额:$0.0万
-
财政年份:2018
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负责人:Priyattam J. Shiromani
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依托单位:
BLR&D Research Career Scientist Award Application
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批准号:9899097
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项目类别:
-
资助金额:$0.0万
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财政年份:2018
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负责人:Priyattam J. Shiromani
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依托单位:
Astroglial Orexin in Sleep Disorders
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批准号:8585663
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项目类别:
-
资助金额:$22.43万
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财政年份:2013
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负责人:Priyattam J. Shiromani
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依托单位:
Astroglial Orexin in Sleep Disorders
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批准号:8706253
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项目类别:
-
资助金额:$18.5万
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财政年份:2013
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负责人:Priyattam J. Shiromani
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依托单位:
Selective Activation of Neurons to Control Narcolepsy
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批准号:8488510
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项目类别:
-
资助金额:$21.35万
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财政年份:2012
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负责人:Priyattam J. Shiromani
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依托单位:
Selective Activation of Neurons to Control Narcolepsy
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批准号:8358785
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项目类别:
-
资助金额:$18.44万
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财政年份:2012
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负责人:Priyattam J. Shiromani
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依托单位:
Sleep Neurobiology and Circuitry
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批准号:8600840
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
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负责人:Priyattam J. Shiromani
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依托单位:
Sleep Neurobiology and Circuitry
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批准号:7929293
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
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负责人:Priyattam J. Shiromani
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依托单位:
Sleep Neurobiology and Circuitry
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批准号:10476016
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
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负责人:Priyattam J. Shiromani
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依托单位:
Sleep Neurobiology and Circuitry
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批准号:8696780
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
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负责人:Priyattam J. Shiromani
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依托单位:
Sleep Neurobiology and Circuitry
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批准号:10045552
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
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负责人:Priyattam J. Shiromani
-
依托单位:
Sleep Neurobiology and Circuitry
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批准号:8196341
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
-
负责人:Priyattam J. Shiromani
-
依托单位:
Sleep Neurobiology and Circuitry
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批准号:10291810
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项目类别:
-
资助金额:$0.0万
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财政年份:2010
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负责人:Priyattam J. Shiromani
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依托单位:
Hypocretin Gene Transfer and Narcolepsy
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批准号:7470399
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项目类别:
-
资助金额:$17.38万
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财政年份:2008
-
负责人:Priyattam J. Shiromani
-
依托单位:
Hypocretin Gene Transfer and Narcolepsy
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批准号:8221225
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项目类别:
-
资助金额:$6.27万
-
财政年份:2008
-
负责人:Priyattam J. Shiromani
-
依托单位:
Hypocretin Gene Transfer and Narcolepsy
-
批准号:7637855
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项目类别:
-
资助金额:$13.62万
-
财政年份:2008
-
负责人:Priyattam J. Shiromani
-
依托单位:
海外基金