| A generally accepted concept of sleep regulation postulates that sleep-wake transitions result from the interaction between circadian and homeostatic processes. The circadian process is ascribed to the activity of the suprachiasmatic nucleus of the hypothalamus, while the mechanism of the homeostatic process are still unclear. In this study we present a concept of hypocretin/orexin-based control of sleep homeostasis. We propose that 1) high frequent impulse activity of the hypocretin/orexin neurons in lateral hypothalamus during wakefulness is sustained by reciprocal excitatory connections with other, e.g. local glutamate neurons; 2) the transition to a silent state (sleep) is going along with a weakening of the hypocretin/orexin synaptic efficacy. These mechanisms constitute a state-dependent, i.e. homeostatic process which can be synchronized with the circadian pacemaker. This concept has been realized in a mathematical model with Hodgkin-Huxley-type neurons and physiology-based synapses. We demonstrate that such homeostatic changes can account for typical alterations of sleep-wake transitions, e.g. introduced by napping, sleep deprivation or alarm clock. In combination with a circadian input, the model mimics the transitions between silent and firing states of hypothalamic neurons in agreement with sleep-wake cycles. Accordingly, under influence of both circadian and homeostatic mechanisms the thalamic neurons undergo transitions between asynchronous tonic firing activity during wakefulness and synchronized busting discharges during sleep. The work was supported by the European Union through the Network of Excellence BioSim contract No LSHB-CT-2004-005137. |
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