First the authors investigated changes in the activity of signalling proteins involved in synaptic potentiation that occur during the early stages of sleep and wakefulness, using synaptoneurosomes (preparations containing enriched pinched-off, resealed presynaptic structures attached to resealed postsynaptic processes) from rat cortex and hippocampus. They found a correlation between the levels and activity of these long-term potentiation (LTP)/long-term depression (LTD)-associated molecules and the amount of sleep the animals had experienced in the preceding 6 hours. A 50% increase in the levels of GluR1, an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-receptor subunit that can be used as a molecular fingerprint of LTP, was observed in the cortical preparations from animals that had been awake for at least 4 hours during the 6-hour period (awake group) compared with those that had slept for at least 4 hours (sleep group). The levels of phosphorylated GluR1, which is associated with membrane incorporation, and of one of the kinases responsible (CAMKII) were also increased, further supporting the idea that glutamatergic synapses might be stronger after periods of wakefulness. In addition, in hippocampal preparations, increased levels of the NMDA (N-methyl-D-aspartate)-receptor subunit NR2A and of phosphorylated glycogen synthase kinase 3β — proteins that have been shown to increase and decrease in concentration during hippocampal LTP and LTD, respectively — were also found in the awake group.
Next they examined electrophysiological correlates of LTP and LTD. Local field potentials (LFPs) have been shown to increase after LTP-inducing procedures in vivo, and the authors showed that after 1 hour of wakefulness the slope of LFPs evoked by electrical stimulation increased significantly, whereas it decreased after 2 hours of sleep. These effects were exacerbated after longer periods of wakefulness or sleep. Similarly, the amplitude of cortical evoked responses increased after wakefulness and decreased after sleep. These effects are not dependent on the time of day, as experiments with rats that had undergone enforced wakefulness yielded similar results.
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