Sleep is required for, and sleep loss impairs, normal hippocampal synaptic
N-methyl-D-aspartate (
NMDA)
glutamate receptor function and expression, hippocampal
NMDA receptor-dependent synaptic plasticity, and hippocampal-dependent memory function. Although sleep is essential, the signals linking sleep to hippocampal function are not known. One potential signal is
growth hormone.
Growth hormone is released during sleep, and its release is suppressed during
sleep deprivation. If
growth hormone links sleep to hippocampal function, then restoration of
growth hormone during
sleep deprivation should prevent adverse consequences of sleep loss. To test this hypothesis, we examined rat hippocampus for spontaneous excitatory synaptic currents in CA1 pyramidal neurons, long-term potentiation in area CA1, and
NMDA receptor subunit
proteins in synaptic membranes. Three days of
sleep deprivation caused a significant reduction in
NMDA receptor-mediated synaptic currents compared with control treatments. When rats were injected with
growth hormone once per day during
sleep deprivation, the loss of
NMDA receptor-mediated synaptic currents was prevented.
Growth hormone injections also prevented the impairment of long-term potentiation that normally follows
sleep deprivation. In addition,
sleep deprivation led to a selective loss of
NMDA receptor 2B (NR2B) from hippocampal synaptic membranes, but normal NR2B expression was restored by
growth hormone injection. Our results identify
growth hormone as a critical mediator linking sleep to normal synaptic function of the hippocampus.