Ghrelin, a circulating gut-hormone, has emerged as an important regulator of growth hormone release and appetite. Ghrelin-immunopositive neurons have also been identified in the hypothalamus with a unique anatomical distribution. Here, we report that ghrelin-labeled neurons receive direct synaptic input from the suprachiasmatic nucleus, the central circadian timekeeper of the brain, and lateral geniculate nucleus, a visual center, and project synaptically to the lateral hypothalamic orexin/hypocretin system, a region of the brain critical for arousal. Hypothalamic ghrelin mRNA oscillates in a circadian pattern peaking in the dark phase prior to the switch from arousal to sleep. Ghrelin inhibits the electrophysiological activity of identified orexin/hypocretin neurons in hypothalamic slices. These observations indicate that the hypothalamic neurons identified by ghrelin immunolabeling may be a key mediator of circadian and visual cues for the hypothalamic arousal system.

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Keywords Arousal, Circadian rhythm, Ghrelin, Hypothalamus, Lateral hypothalamus
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Journal Molecular Metabolism
Horvath, T.L. (Tamas L.), Abizaid, A, Dietrich, M.O. (Marcelo O.), Li, Y. (Ying), Takahashi, J.S. (Joseph S.), & Bass, J. (Joseph). (2012). Ghrelin-immunopositive hypothalamic neurons tie the circadian clock and visual system to the lateral hypothalamic arousal center. Molecular Metabolism, 1(1-2), 79–85. doi:10.1016/j.molmet.2012.08.003