Abstract:
Propofol is the most widely used intravenous general anesthetic; however, the neuronal circuits that mediate its anesthetic effects are still poorly understood. Glutamatergic neurons in the lateral hypothalamus have been reported to be involved in maintenance of arousal and consciousness. Using Vglut2-Cre transgenic mice, we recorded this group of cells specifically and found that propofol can directly inhibit the glutamatergic neurons, and enhance inhibitory synaptic inputs on these cells, thereby reducing neuronal excitability. Through chemogenetic interventions, we found that inhibition of these neurons increased the duration of propofol-induced anesthesia and reduced movement in the animals after the recovery of right reflex. In contrast, activating this group of cells reduced the duration of propofol anesthesia and increased the animals\' locomotor activity after the recovery of right reflex. These results suggest that propofol-induced anesthesia involves the inhibition of glutamatergic neurons in the lateral hypothalamus.
摘要:
丙泊酚是最广泛使用的静脉全身麻醉药;然而,介导其麻醉作用的神经元回路仍然知之甚少。据报道,下丘脑外侧的谷氨酸能神经元参与了唤醒和意识的维持。使用Vglut2-Cre转基因小鼠,我们专门记录了这组细胞,发现异丙酚可以直接抑制谷氨酸能神经元,增强这些细胞的抑制性突触输入,从而降低神经元兴奋性。通过化学干预,我们发现,这些神经元的抑制增加了丙泊酚诱导的麻醉持续时间,并减少了动物右反射恢复后的运动.相比之下,激活这组细胞可减少丙泊酚麻醉的持续时间,并在右反射恢复后增加动物的运动活动。这些结果表明,异丙酚诱导的麻醉涉及对下丘脑外侧谷氨酸能神经元的抑制。