Abstract
Converging electrophysiological, molecular, and ultrastructural evidence
supports the hypothesis that sleep promotes a net decrease in excitatory
synaptic strength, counteracting the net synaptic potentiation caused by
ongoing learning during waking. However, several outstanding questions
about sleep-dependent synaptic weakening remain. Here, we address some
of these questions by using two established molecular markers of
synaptic strength, the levels of the calcium-permeable AMPA
(Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid) receptors
containing the GluA1 subunit, and the phosphorylation of GluA1 at serine
845. We previously found that, in the rat cortex and hippocampus, these
markers are lower after 6-8 hours of sleep than after the same time
spent awake. Here, we measure GluA1 expression in mouse cortex after 5
hours of either sleep, sleep deprivation, recovery sleep after sleep
deprivation, or selective REM sleep deprivation (32 C57BL/B6 adult mice,
16 females). We find that relative to after sleep deprivation, synaptic
GluA1 expression is lower after sleep independent of whether the mice
were allowed to enter REM sleep. Moreover, 5 hours of recovery sleep
following acute sleep deprivation are enough to renormalize GluA1
expression. In a pilot study in old mice (12 C57BL/B6 male mice,
20-month-old) we also find that GluA1 expression is high after sleep
deprivation and low after sleep and recovery sleep. Thus, the
renormalization of GluA1 expression crucially relies on NREM sleep and
can occur in a few hours of sleep after acute sleep deprivation.
Moreover, as measured by GluA1 expression, it appears that
sleep-dependent synaptic weakening is unaffected by aging.