Pharmacogenetic modulation of orexin neurons alters sleep/wakefulness states in mice.
Pharmacogenetic modulation of orexin neurons alters sleep/wakefulness states in mice.
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DOI：
10.1371/journal.pone.0020360
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sakurai T
中科院分区：
文献类型：
--
作者：
Sasaki K;Suzuki M;Mieda M;Tsujino N;Roth B;Sakurai T
表达神经肽食欲素的下丘脑神经元与睡眠和觉醒的控制密切相关。尽管食欲素神经元的活性被认为受到各种神经元输入以及体液因素的影响，但在完整动物中这些神经元活性变化的直接后果在很大程度上是未知的。因此，我们研究了食欲素神经元特异性药物遗传学调制在体内的影响，通过一种新的方法称为设计师受体专门激活的设计师药物的方法（DREADD）。使用这个系统，我们成功地激活和抑制食欲素神经元，通过Fos染色测量。EEG和EMG记录表明，食欲素神经元的兴奋显着增加了清醒时间，并减少了非快速眼动（NREM）和快速眼动（REM）睡眠时间。食欲素神经元的抑制减少了觉醒时间，增加了NREM睡眠时间。这些发现清楚地表明，食欲素神经元活动的变化可以改变动物的行为状态，也验证了这种操纵清醒、自由移动动物神经元活动的新方法。
Hypothalamic neurons expressing neuropeptide orexins are critically involved in the control of sleep and wakefulness. Although the activity of orexin neurons is thought to be influenced by various neuronal input as well as humoral factors, the direct consequences of changes in the activity of these neurons in an intact animal are largely unknown. We therefore examined the effects of orexin neuron-specific pharmacogenetic modulation in vivo by a new method called the Designer Receptors Exclusively Activated by Designer Drugs approach (DREADD). Using this system, we successfully activated and suppressed orexin neurons as measured by Fos staining. EEG and EMG recordings suggested that excitation of orexin neurons significantly increased the amount of time spent in wakefulness and decreased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep times. Inhibition of orexin neurons decreased wakefulness time and increased NREM sleep time. These findings clearly show that changes in the activity of orexin neurons can alter the behavioral state of animals and also validate this novel approach for manipulating neuronal activity in awake, freely-moving animals.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
3.4
作者：
Yoshida, Y;Fujiki, N;Nishino, S
通讯作者：
Nishino, S
影响因子：
5.3
作者：
Lee, MG;Hassani, OK;Jones, BE
通讯作者：
Jones, BE
DOI：
10.1073/pnas.0811126106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Matsuki, Taizo;Nomiyama, Mika;Sakurai, Takeshi
通讯作者：
Sakurai, Takeshi
影响因子：
16.2
作者：
Yamanaka, A;Beuckmann, CT;Sakurai, T
通讯作者：
Sakurai, T