Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
J Neurosci. 2013 Jun 5;33(23):9743-51. doi: 10.1523/JNEUROSCI.0499-13.2013.
Narcolepsy is characterized by chronic sleepiness and cataplexy, episodes of profound muscle weakness that are often triggered by strong, positive emotions. Narcolepsy with cataplexy is caused by a loss of orexin (also known as hypocretin) signaling, but almost nothing is known about the neural mechanisms through which positive emotions trigger cataplexy. Using orexin knock-out mice as a model of narcolepsy, we found that palatable foods, especially chocolate, markedly increased cataplexy and activated neurons in the medial prefrontal cortex (mPFC). Reversible suppression of mPFC activity using an engineered chloride channel substantially reduced cataplexy induced by chocolate but did not affect spontaneous cataplexy. In addition, neurons in the mPFC innervated parts of the amygdala and lateral hypothalamus that contain neurons active during cataplexy and that innervate brainstem regions known to regulate motor tone. These observations indicate that the mPFC is a critical site through which positive emotions trigger cataplexy.
发作性睡病的特征是慢性嗜睡和猝倒，即强烈的正面情绪引发的深度肌肉无力发作。猝倒伴发发作性睡病是由于食欲素（也称为下丘脑分泌素）信号缺失所致，但人们对正面情绪引发猝倒的神经机制几乎一无所知。我们利用食欲素敲除小鼠作为发作性睡病模型发现，美味食物，尤其是巧克力，明显增加猝倒发作的频率并激活了内侧前额叶皮质（mPFC）的神经元。使用工程化氯离子通道可逆性地抑制 mPFC 的活动，可显著减少巧克力诱发的猝倒，但不影响自发性猝倒。此外，mPFC 的神经元投射到杏仁核和外侧下丘脑的某些区域，这些区域包含在猝倒期间活跃的神经元，并投射到已知调节运动张力的脑干区域。这些观察结果表明，mPFC 是通过积极情绪引发猝倒的关键部位。
