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-2009GliaGlia:Neurons = 10:1Traditionally 3 types of Glia A
2、strocytes Oligodendrocytes MicrogliaRecently NG2+ Cells Added“Brain Glue”!?Functions2009 McGraw-Hill Companies, From “http:/ By GFAP (Glial Fibrillary Acidic Protein) ExpressionHighly Ramified, Intracellular CouplingFunctions: Metabolic Roles K+ Buffering Blood Brain Barrier Precursor Cells?2007 The
3、 University of Utah, Genetic Science Learning Center Occupy defined, non-overlapping domains Hippocampus 100,000 Synapses Bushong et al., 2002 Cortex 2-8 Somata 300-600 Dendrites Halassa et al, 2007Bushong EA, Martone ME, Jones YZ, Ellisman MH Protoplasmic astrocytes in CA1 stratum radiatum occupy s
4、eparate anatomical domains. J Neurosci 22; 183-92, 2002 Copyright 2007 Society for NeuroscienceHalassa, M. M. et al. J. Neurosci. 2007;27:6473-6477Figure 2. One astrocyte enwraps several neuronal somataThe Tripartite SynapseFilipodia and Lamellipodia Envelop SynapseClearance of NeurotransmittersRece
5、ptorsCalcium TransientsGliotransmissionAnd NowTHE PAPEROutline GFAP Driven dnSNARE Attenuate exocytotic GliotransmissionAssessed effects on Sleep and EEGPharmacological experiments to characterise cause of these effectsObject recognition task to examine effects on sleep deprivation induced memory im
6、pairmentsdnSNARETetracycline 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 transgeneNo significant alterations to total sleep time, REM time, NREM
7、 time, or 24-hour EEG spectra between groups Open Circles/Bars: Wild Type Closed Circles/Bars: dnSNAREDuring 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)Effe
8、cts of Sleep Deprivation on MemorySleep 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
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