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Molecular Biology and Genetics of Sleep
Chiara Cirelli, M.D., Ph.D. Department of Psychiatry
University of Wisconsin/Madison
Molecular biology studies (transcriptomics) Genetic studies
Molecular biology Studies (transcriptomics)
Genetic studies
Molecular changes: microarray analysis
sleep sleep
Molecular changes: microarray analysis
sleep sleep
10-15,000 mRNAs analyzed
state-dependent expression in 1-5% of all
present probes
wake and sleep genes belong to different
functional categories
Functional categories of sleep and wake genes
Cirelli, Nature Review Neuroscience 2009
Molecular state-dependent changes
energy metabolism
cellular stress response
synaptic potentiation
Waking
Sleep
Genes involved in synaptic potentiation are upregulated during wake
Cirelli et al. Science 1996, J Neurosci 2000, Neuron 2004
6h of sleep 6h of waking
P-CREB
rat cerebral cx
Cirelli et al, J Neurosci 2000, Neuron 2004; Hanlon E, unpublished
Genes involved in synaptic potentiation are upregulated during wake
Other plasticity-related genes upregulated in wake: NGFI-A, Homer, Narp, CamKII, Arc
6h of sleep 6h of waking
BDNF
rat cerebral cx
GluR1-AMPA receptors are the best established molecular markers of synaptic strength
Decrease in synaptic strength in vivo / LTD in vitro
Monocular deprivation and visual cx (Heynen et al., Nature Neurosci 2003)
Increase in synaptic strength in vivo / LTP in vitro
Fear conditioning and amygdala (Rumpel et al. Science 2005) Avoidance learning and hippocampus (Whitlock et al. Science 2006) Emotional memory and hippocampus (Hu et al. Cell 2007)
P-S845 P-S845 P-S831 GluR1
Increased expression of synaptic GluR1 during wake
Vyazovskiy et al., Nature Neurosci 2008
Synapto- neurosomes
SD S W
Molecular state-dependent changes
energy metabolism
cellular stress response
synaptic potentiation
Waking
Sleep
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