Sleep-wake transitions result from the interaction between circadian and homeostatic processes as suggested by the two process model. The circadian process is ascribed to the activity of the suprachiasmatic nucleus of the hypothalamus, while the mechanism of the homeostatic process is still unclear.

In this study we present a concept of hypocretin/orexin (hcrt/ox)-based control of sleep homeostasis. We propose that 1) high frequent impulse activity of the hcrt/ox neurons during the wake state is sustained by reciprocal excitatory connections with other, e.g. local glutamate neurons; 2) the transition to a silent state is going along with a weakening of the synaptic efficacy of hcrt/ox. 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. The model offers a new approach for further evaluation of the physiological, especially homeostatic mechanisms of sleep-wake cycles on the basis of neuronal activity and synaptic transmission.

The work was supported by the European Union through the Network of Excellence BioSim contract No LSHB-CT-2004–005137.