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1、“Astrocytic Modulation of Sleep Homeostasis and Cognitive Consequences of Sleep Loss”,Michael M.Halassa,Cedrick Florian,Tommaso Fellin,James R.Munoz,So-Young Lee,Ted Abel,Philip G.Haydon,and Marcos G.Frank,Journal Club,10-February-2009,Glia,Glia:Neurons=10:1Traditionally 3 types of GliaAstrocytesOli
2、godendrocytesMicrogliaRecently NG2+Cells Added“Brain Glue”!?Functions,2009 McGraw-Hill Companies,From“http:/,Astrocytes!,Defined By GFAP(Glial Fibrillary Acidic Protein)ExpressionHighly Ramified,Intracellular CouplingFunctions:Metabolic RolesK+BufferingBlood Brain BarrierPrecursor Cells?,2007 The Un
3、iversity of Utah,Genetic Science Learning Center,Occupy defined,non-overlapping domainsHippocampus100,000 SynapsesBushong et al.,2002Cortex2-8 Somata300-600 DendritesHalassa et al,2007,Bushong EA,Martone ME,Jones YZ,Ellisman MH Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomic
4、al domains.J Neurosci 22;183-92,2002,Copyright 2007 Society for Neuroscience,Halassa,M.M.et al.J.Neurosci.2007;27:6473-6477,Figure 2.One astrocyte enwraps several neuronal somata,The Tripartite Synapse,Filipodia and LamellipodiaEnvelop SynapseClearance of NeurotransmittersReceptorsCalcium Transients
5、Gliotransmission,And Now,THE PAPER,Outline,GFAP Driven dnSNAREAttenuate exocytotic GliotransmissionAssessed effects on Sleep and EEGPharmacological experiments to characterise cause of these effectsObject recognition task to examine effects on sleep deprivation induced memory impairments,dnSNARE,Tet
6、racycline Transactivator(tTA)under GFAP promoterdnSNARE under tet.O promotertTA activates tet.O and drives expression of dnSNAREConditional supression:Doxycycline in the diet 50%cortical astrocytes express transgene,No significant alterations to total sleep time,REM time,NREM time,or 24-hour EEG spe
7、ctra between groupsOpen Circles/Bars:Wild TypeClosed Circles/Bars:dnSNARE,During the Light Phase,(C-G,After 6-Hour Sleep Deprivation Protocol),Mechanism assumed to be inhibition of extracellular adenosine build-up,acting via A1RTests:Occlusion:(G)Mimic:(H)and(I),Effects of Sleep Deprivation on Memor
8、y,Sleep deprivation,linked to impaired memory and cognitive functionNovel Object Recognition task sensitive to the effects of“sleep pressure”,dnSNARE/A1R antagonism protects against Sleep deprivation induced impairmentsdnSNARE RatsNo difference in exploration timeNo differences in AnxietyNo Motor impairmentNo contextual fear conditioning impairmentsNot an Effect of Sleep,rather Sleep Pressure/Adenosine,
