“Astrocytic Modulation of Sleep Homeostasis and Cognitive “睡眠的平衡和认知的星形胶质细胞调制课件

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,“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,“Astrocytic Modulation of Slee,Glia,Glia:Neurons=10:1,Traditionally 3 types of Glia,Astrocytes,Oligodendrocytes,Microglia,Recently NG2+Cells Added,“Brain Glue”!?,Functions,200,9 McGraw-Hill Companies,From“http:/ M,Astrocytes!,Defined By GFAP(Glial Fibrillary Acidic Protein)Expression,Highly Ramified,Intracellular Coupling,Functions:,Metabolic Roles,K,+,Buffering,Blood Brain Barrier,Precursor Cells?,2007 The University of Utah,Genetic Science Learning Center,Astrocytes!Defined By GFAP(Gl,Occupy defined,non-overlapping domains,Hippocampus,100,000 Synapses,Bushong et al.,2002,Cortex,2-8 Somata,300-600 Dendrites,Halassa et al,2007,Bushong EA,Martone ME,Jones YZ,Ellisman MH,Protoplasmic astrocytes in CA1,stratum radiatum occupy separate anatomical domains.,J Neurosci,22;183-92,2002,Bushong EA,Martone ME,Jones,Copyright 2007 Society for Neuroscience,Halassa,M.M.et al.J.Neurosci.2007;27:6473-6477,Figure 2.One astrocyte enwraps several neuronal somata,Copyright 2007 Society for Ne,The Tripartite Synapse,Filipodia and Lamellipodia,Envelop Synapse,Clearance of Neurotransmitters,Receptors,Calcium Transients,Gliotransmission,The Tripartite SynapseFilipodi,And Now,THE PAPER,And NowTHE PAPER,Outline,GFAP Driven dnSNARE,Attenuate exocytotic Gliotransmission,Assessed effects on Sleep and EEG,Pharmacological experiments to characterise cause of these effects,Object recognition task to examine effects on sleep deprivation induced memory impairments,OutlineGFAP Driven dnSNARE,dnSNARE,Tetracycline Transactivator(tTA)under GFAP promoter,dnSNARE under tet.O promoter,tTA activates tet.O and drives expression of dnSNARE,Conditional supression:,Doxycycline in the diet,50%cortical astrocytes express transgene,dnSNARETetracycline Transactiv,No significant alterations to total sleep time,REM time,NREM time,or 24-hour EEG spectra between groups,Open Circles/Bars:Wild Type,Closed Circles/Bars:dnSNARE,No significant alterations to,“Astrocytic Modulation of Sleep Homeostasis and Cognitive“睡眠的平衡和认知的星形胶质细胞调制课件,During the Light Phase,(C-G,After 6-Hour Sleep Deprivation Protocol),During the Light Phase(C-G,A,Mechanism assumed to be inhibition of extracellular adenosine build-up,acting via A,1,R,Tests:,Occlusion:(G),Mimic:(H)and(I),“Astrocytic Modulation of Sleep Homeostasis and Cognitive“睡眠的平衡和认知的星形胶质细胞调制课件,Effects of Sleep Deprivation on Memory,Sleep deprivation,linked to impaired memory and cognitive function,Novel Object Recognition task sensitive to the effects of,“,sleep pressure,”,Effects of Sleep Deprivation o,dnSNARE/A,1,R antagonism protects against Sleep deprivation induced impairments,dnSNARE Rats,No difference in exploration time,No differences in Anxiety,No Motor impairment,No contextual fear conditioning impairments,Not an Effect of Sleep,rather Sleep Pressure/Adenosine,“Astrocytic Modulation of Sleep Homeostasis and Cognitive“睡眠的平衡和认知的星形胶质细胞调制课件,