Time- and Behavioral State-Dependent Changes in Posterior Hypothalamic GABAA Receptors Contribute to the Regulation of Sleep
Figure 8
A model of the dynamic interactions involving GABAA receptors, GABA stores and neuronal activity occurring within the wake-promoting region of the posterior hypothalamus supported by the findings from the present study.
We propose that the availability of GABAA receptors present in wake-promoting neurons increases with the duration of wakefulness, and so does the level of GABA in presynaptic terminals. A: when the combined strength of this potential inhibitory action is sufficiently high, sleepiness develops and sleep may ensue provided that it is not opposed by circadian mechanisms and/or excessive sensory stimulation. B: when wakefulness is extended by sleep deprivation, GABAA receptors in wake-promoting neurons and GABA stores increase above the normal levels typical of the end of the active period. This may represent a neurochemical substrate of the increased drive for sleep. Under this condition, sleep occurs more readily and is deeper in the sense that it is more resistant to awakening stimuli. C: at the end of a complete rest/sleep period, the availability of GABAA receptors on wake-promoting neurons is diminished due to their prolonged stimulation during sleep, and GABA stores are depleted. As a result, sleep-maintenance mechanisms are weakened and arousal followed by sustained wakefulness can readily occur. Our results suggest that GABAA receptors containing β1, β3 and ε subunits located on wake-active posterior hypothalamic neurons are particularly important in this model because the levels of these subunits (mRNA and/or protein) vary with the pressure for sleep and show limited or no circadian time dependence.