Nagoya University · 신경과학
아키후로 ヤマナ카 교수의 연구실은 뇌의 수면-각성 조절과 에너지 균형 유지를 담당하는 옵레린 신경세포의 기능과 신호전달 메커니즘을 중심으로 연구를 진행하고 있습니다. 특히 옵레린 신경세포의 활성화 및 억제를 조절하는 신경전달물질(세로토닌, 도파민, 노르에피네프린, CCK 등)과 신경전달 물질 수용체의 작용 기전을 전기생리학적 및 유전자 조작 기법을 통해 규명하고 있습니다. 또한, 옵레린 신경세포가 수면-각성 리듬과 대사 조절에 미치는 영향을 옵토제네틱스와 약리유전학 기법을 활용해 실시간으로 분석하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Both orexin and serotonin (5-HT) have important roles in the regulation of sleep-wakefulness, as well as in feeding behavior. We examined the effects of 5-HT on orexin/hypocretin neurons, using hypothalamic slices prepared from orexin/enhanced green fluorescent protein (EGFP) transgenic mice in which EGFP is expressed exclusively in orexin neurons. Patch-clamp recording from EGFP-expressing cells showed that 5-HT hyperpolarized all orexin neurons in a concentration-dependent manner. The response
Orexin A and B are neuropeptides implicated in the regulation of sleep/wakefulness and energy homeostasis. The regulatory mechanism of the activity of orexin neurons is not precisely understood. Using transgenic mice in which orexin neurons specifically express yellow cameleon 2.1, we screened for factors that affect the activity of orexin neurons (a total of 21 peptides and six other factors were examined) and found that a sulfated octapeptide form of cholecystokinin (CCK-8S), neurotensin, oxyt
Orexin neurons in the hypothalamus regulate energy homeostasis by coordinating various physiological responses. Past studies have shown the role of the orexin peptide itself; however, orexin neurons contain not only orexin but also other neurotransmitters such as glutamate and dynorphin. In this study, we examined the physiological role of orexin neurons in feeding behavior and metabolism by pharmacogenetic activation and chronic ablation. We generated novel orexin-Cre mice and utilized Cre-depe
Orexin neurons (hypocretin neurons) have a critical role in the regulation of sleep/wakefulness, especially in the maintenance of arousal. Here, we revealed that orexin neurons are directly and indirectly activated by orexin via the orexin 2 receptor (OX2R). Orexin B (1 μM) induced depolarization in orexin neurons, which was still observed in the presence of TTX (1 μM), AP-5 (50 μM), and CNQX (20 μM). In addition, orexin B induced inward currents in the presence of TTX, suggesting a direct activ
We reported elsewhere that orexin neurons are directly hyperpolarized by noradrenaline (NA) and dopamine. In the present study, we show that NA, dopamine, and adrenaline all directly hyperpolarized orexin neurons. This response was inhibited by the alpha2 adrenergic receptor (alpha2-AR) antagonist, idazoxan or BRL44408, and was mimicked by the alpha2-AR-selective agonist, UK14304. A low concentration of Ba2+ inhibited NA-induced hyperpolarization, which suggests that activation of G protein coup
In mammals, the daily rhythms of physiological functions are timed by the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the importance of the SCN for the regulation of sleep/wakefulness has been suggested, little is known about the neuronal projections from the SCN, which regulate sleep/wakefulness. Here, we show that corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus mediate circadian rhythms in the SCN a
