Zhang Shao-Qi, Xia Zhi-Xuan, Deng Qiao, Yang Ping-Fen, Long Li-Hong, Wang Fang, Chen Jian-Guo
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei, 430030, China.
The Research Center for Depression, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China.
Neurobiol Stress. 2022 Apr 22;18:100453. doi: 10.1016/j.ynstr.2022.100453. eCollection 2022 May.
Repeated vagus nerve stimulation (rVNS) exerts anxiolytic effect by activation of noradrenergic pathway. Centrolateral amygdala (CeL), a lateral subdivision of central amygdala, receives noradrenergic inputs, and its neuronal activity is positively correlated to anxiolytic effect of benzodiazepines. The activation of β-adrenergic receptors (β-ARs) could enhance glutamatergic transmission in CeL. However, it is unclear whether the neurobiological mechanism of noradrenergic system in CeL mediates the anxiolytic effect induced by rVNS. Here, we find that rVNS treatment produces an anxiolytic effect in male rats by increasing the neuronal activity of CeL. Electrophysiology recording reveals that rVNS treatment enhances the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR)-mediated excitatory neurotransmission in CeL, which is mimicked by β-ARs agonist isoproterenol or blocked by β-ARs antagonist propranolol. Moreover, chemogenetic inhibition of CeL neurons or pharmacological inhibition of β-ARs in CeL intercepts both enhanced glutamatergic neurotransmission and the anxiolytic effects by rVNS treatment. These results suggest that the amplified AMPAR trafficking in CeL via activation of β-ARs is critical for the anxiolytic effects induced by rVNS treatment.
重复迷走神经刺激（rVNS）通过激活去甲肾上腺素能通路发挥抗焦虑作用。中央杏仁核外侧亚核（CeL）接受去甲肾上腺素能输入，其神经元活动与苯二氮䓬类药物的抗焦虑作用呈正相关。β-肾上腺素能受体（β-ARs）的激活可增强CeL中的谷氨酸能传递。然而，尚不清楚CeL中去甲肾上腺素能系统的神经生物学机制是否介导rVNS诱导的抗焦虑作用。在此，我们发现rVNS治疗通过增加CeL的神经元活动在雄性大鼠中产生抗焦虑作用。电生理学记录显示，rVNS治疗增强了CeL中α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）介导的兴奋性神经传递，β-ARs激动剂异丙肾上腺素可模拟这种作用，而β-ARs拮抗剂普萘洛尔可阻断这种作用。此外，CeL神经元的化学遗传学抑制或CeL中β-ARs的药理学抑制均阻断了rVNS治疗增强的谷氨酸能神经传递和抗焦虑作用。这些结果表明，通过激活β-ARs使CeL中AMPAR转运增加对于rVNS治疗诱导的抗焦虑作用至关重要。
