Nature Reviews Neuroscience 9, 166-167 (March 2008) | doi:10.1038/nrn2348
Synaptic plasticity: Rise and shine (we are all morning people!)
Monica Hoyos Flight
The effects of sleep on learning and memory are well documented — many studies have shown a decline in the performance of memory tasks following sleep deprivation — yet the effects of sleep on synaptic plasticity are not well understood. The latest findings from Giulio Tononi's group, published in Nature Neuroscience, suggest that sleep performs a homeostatic function by resetting synaptic potentiation.
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 -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 3 — 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.
Interestingly, it was easier to induce LTP in rats shortly after a period of sleep than after several hours of wakefulness, suggesting that prolonged wakefulness might saturate neuronal circuits and that sleep performs a restorative function by correcting the imbalance that occurs during wake time.
This study shows that both molecular and electrophysiological indicators of synaptic efficacy in the cortex and hippocampus change as a function of wake and sleep history. Whereas wakefulness favours synaptic potentiation, sleep appears to favour net synaptic depression. Although the effects await examination at the level of the synapse, these findings indicate that sleep has a homeostatic influence that is important for resetting neuronal excitability and facilitating plasticity in our waking hours.