Circadian and dark-pulse activation of orexin/hypocretin neurons

Dec 6, 2008Molecular brain

Daily rhythms and brief darkness stimulate brain cells that control wakefulness

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Abstract

Mice showed pronounced circadian patterns in orexin neuronal activation even in constant light conditions.

The interaction between circadian and homeostatic neural circuits regulates daily sleep and wake rhythms.
Orexin neurons in the hypothalamus are activated prior to sustained wheel-running activity, indicating their role in promoting arousal.
A 6-hour dark pulse during the subjective day activated orexin-containing neurons while suppressing activity in the suprachiasmatic nuclei.
Dark pulse exposure at night did not reset behavioral rhythms and reduced activation in orexin neurons.
These findings suggest a novel circadian control of orexin neuron activation and their involvement in resetting the circadian clock.

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Temporal control of brain and behavioral states emerges as a consequence of the interaction between circadian and homeostatic neural circuits. This interaction permits the daily rhythm of sleep and wake, regulated in parallel by circadian cues originating from the suprachiasmatic nuclei (SCN) and arousal-promoting signals arising from the orexin-containing neurons in the tuberal hypothalamus (TH). Intriguingly, the SCN circadian clock can be reset by arousal-promoting stimuli while activation of orexin/hypocretin neurons is believed to be under circadian control, suggesting the existence of a reciprocal relationship. Unfortunately, since orexin neurons are themselves activated by locomotor promoting cues, it is unclear how these two systems interact to regulate behavioral rhythms. Here mice were placed in conditions of constant light, which suppressed locomotor activity, but also revealed a highly pronounced circadian pattern in orexin neuronal activation. Significantly, activation of orexin neurons in the medial and lateral TH occurred prior to the onset of sustained wheel-running activity. Moreover, exposure to a 6 h dark pulse during the subjective day, a stimulus that promotes arousal and phase advances behavioral rhythms, activated neurons in the medial and lateral TH including those containing orexin. Concurrently, this stimulus suppressed SCN activity while activating cells in the median raphe. In contrast, dark pulse exposure during the subjective night did not reset SCN-controlled behavioral rhythms and caused a transient suppression of neuronal activation in the TH. Collectively these results demonstrate, for the first time, pronounced circadian control of orexin neuron activation and implicate recruitment of orexin cells in dark pulse resetting of the SCN circadian clock.

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Circadian and dark-pulse activation of orexin/hypocretin neurons

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