“The study to reveal mechanism of narcolepsy symptoms by the adoptive circuit shift after ablation of orexin neurons”

We use optogenetics or pharmacogenetics to control the activity of targeted neurons in vivo. Alternatively the fate of targeted neurons is controlled to reveal physiological role of these targeted neurons. We focused on instinctive behaviors such as feeding, drinking, sexual behavior and sleep/wakefulness regulation. In this study, we study the role of orexin neurons in the hypothalamus. These neurons are implicated in the regulation of sleep/wakefulness. Specific degeneration of these neurons is caused by sleep disorder Narcolepsy. Symptom of Narcolepsy is excessive day-time sleepiness, sudden muscle weakness called cataplexy. Not only these symptoms,Narcolepsy patients show abnormality of metabolism. Recently we generated new narcolepsy model mice which enable ablate orexin neurons in specific timing. These mice perfectly mimic all symptoms seen in human Narcolepsy. The aim of this study is to reveal mechanism of narcolepsy symptoms by the adoptive circuit shift after ablation of orexin neurons.We use optogenetics or pharmacogenetics to control the activity of targeted neurons in vivo. Alternatively the fate of targeted neurons is controlled to reveal physiological role of these targeted neurons. We focused on instinctive behaviors such as feeding, drinking, sexual behavior and sleep/wakefulness regulation. In this study, we study the role of orexin neurons in the hypothalamus. These neurons are implicated in the regulation of sleep/wakefulness. Specific degeneration of these neurons is caused by sleep disorder Narcolepsy. Symptom of Narcolepsy is excessive day-time sleepiness, sudden muscle weakness called cataplexy. Not only these symptons,Narcolepsy patients show abnormality of metabolism. Recently we generated new narcolepsy model mice which enable ablate orexin neurons in specific timing. These mice perfectly mimic all symptoms seen in human Narcolepsy. The aim of this study is to reveal mechanism of narcolepsy symptoms by the adoptive circuit shift after ablation of orexin neurons.

 
Recent Publications
1. Tabuchi S, Tsunematsu T, Black SW, Tominaga M, Maruyama M, Takagi K, Minokoshi Y, Sakurai T, Kilduff TS, Yamanaka A (2014) Conditional ablation of orexin/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function. J Neurosci 34:6495-6509.
2. Tsunematsu T, Ueno T, Tabuchi S, Inutsuka A, Tanaka KF, Hasuwa H, Kilduff TS, Terao A, Yamanaka A (2014) Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. J Neurosci 34:6896-6909.
3. Inutsuka A, Inui A, Tabuchi S, Tsunematsu T, Lazarus M, Yamanaka A (2014) Concurrent and robust regulation of feeding behaviors and metabolism by orexin neurons. Neuropharmacology 85:451-460.

Posted:2016/03/10