| Autor: |
Matsuki, Taizo, Nomiyama, Mika, Takahira, Hitomi, Hirashima, Noriko, Kunita, Satoshi, Takahashi, Satoru, Yagami, Ken-ichi, KiIduff, Thomas S., BettIer, Bernhard, Yanagisawa, Masashi, Sakurai, Takeshi |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 3/17/2009, Vol. 106 Issue 11, p4459-4464, 6p, 4 Graphs |
| Abstrakt: |
Hypothalamic neurons that contain the neuropeptide orexin (hypocretin) play important roles in the regulation of sleep/wake. Here we analyze the in vivo and in vitro phenotype of mice lacking the GABA[subB1] gene specifically in orexin neurons (oxGKO mice) and demonstrate that GABA[subB] receptors on orexin neurons are essential in stabilizing and consolidating sleep/wake states. In oxGKO brain slices, we show that the absence of GABA[subB] receptors decreases the sensitivity of orexin neurons to both excitatory and inhibitory inputs because of augmented GABA[subA]-mediated inhibition that increases the membrane conductance and shunts postsynaptic currents in these neurons. This increase in GABA[subA]-mediated inhibitory tone is apparently the result of an orexin receptor type 1-mediated activation of local GABAergic interneurons that project back onto orexin neurons. oxGKO mice exhibit severe fragmentation of sleep/wake states during both the light and dark periods, without showing an abnormality in total sleep time or signs of cataplexy. Thus. GABA[subB] receptors on orexin neurons are crucial in the appropriate control of the orexinergic tone through sleep/wake states, thereby stabilizing the state switching mechanisms. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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