Annual Meeting of the Swiss Physiological Society, October 6, 2005
Asher-Hess Prize
Abstracts selected for oral presentation
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EX VIVO CHANGES IN HIPPOCAMPAL LONG TERM SYNAPTIC PLASTICITY AFTER SLEEP DEPRIVATION.

C. Kopp , J.R. Nicholson and A. Luthi.

Biozentrum, Division Pharmacology-Neurobiology, University of Basel.

Why do we sleep? Accumulating evidence suggests that sleep favours learning and memory. However, the negative effects of sleep loss on memory and long-term potentiation and depression (LTP-LTD), established cellular models for memory consolidation, are still controversial. In particular, it remains difficult to disentangle effects of sleep loss from confounding factors of the sleep deprivation (SD) procedure, such as stress.

Here, we investigated the frequency dependence of synaptic plasticity after total, stress-free SD in young adult mice. Sleep was prevented by stimulating the natural curiosity of the mice with an enlarged environment and nesting material, while direct manipulation of the animals was strictly avoided. The procedure was halted when the mice no longer reacted to the stimuli and fell asleep, requiring approximately 4 hours. Control (CTRL) mice were left undisturbed and euthanized at the same time of day as sleep-deprived ones. The absence of stress after SD was confirmed by plasma corticosterone radioimmunoassay, which showed similar, low levels in both groups. Field potentials (FPs), representing the response of neuronal populations to afferent stimulation, were recorded in the Schaffer collateral-CA1 pathway of parasagittal hippocampal slices. LTP induced by two 1-sec trains at 100 Hz was markedly reduced in SD slices, although repeated tetanic stimulations induced similar LTP in both groups. Synaptic plasticity was further tested after different low frequency stimulations (LFS; 900 pulses, 1-10 Hz). SD induced a rightward shift in the S-shaped frequency dependence of synaptic plasticity. Similar effects were found after SD in whisker-trimmed mice, excluding prolonged somatosensory stimuli as the principal cause mediating the effects of SD. LTP and 1-Hz LFS-induced LTD were NMDA receptor-dependent in CTRL slices. When assessing the cellular mechanisms underlying the actions of SD, we found that the NR2B-specific NMDA receptor antagonist ifenprodil reduced pharmacologically isolated NMDA receptor-mediated FPs by approximately 50% in SD compared to CTRL slices, suggesting that SD-induced changes in synaptic plasticity may involve a rapid change in the subunit composition of synaptic NMDA receptors. Finally, 3 hours of recovery sleep after SD, known to completely dissipate compensatory sleep processes, restored normal synaptic plasticity. The results demonstrate that sleep loss rapidly and reversibly modulates bidirectional synaptic plasticity, independent of stress and somatosensory stimuli.