Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia

作者：Fuyang Cao, Yongxin Guo, Shuting Guo, Xinyu Hao, Lujia Yang, Jiangbei Cao, Zhikang Zhou, Weidong Mi, Tong Li · 发表于：CNS Neuroscience & Therapeutics · 年份：2024 · DOI：10.1111/cns.14675 · 被引用次数：9 · 研究领域：Anesthesia and Sedative Agents、Anesthesia and Neurotoxicity Research、Neural dynamics and brain function

Abstract Aims General anesthesia has been used in surgical procedures for approximately 180 years, yet the precise mechanism of anesthetic drugs remains elusive. There is significant anatomical connectivity between the ventral tegmental area (VTA) and the prelimbic cortex (PrL). Projections from VTA dopaminergic neurons (VTA DA ) to the PrL play a role in the transition from sevoflurane anesthesia to arousal. It is still uncertain whether the prelimbic cortex pyramidal neuron (PrL Pyr ) and its projections to VTA (PrL Pyr ‐VTA) are involved in anesthesia‐arousal regulation. Methods We employed chemogenetics and optogenetics to selectively manipulate neuronal activity in the PrL Pyr ‐VTA pathway. Electroencephalography spectra and burst‐suppression ratios (BSR) were used to assess the depth of anesthesia. Furthermore, the loss or recovery of the righting reflex was monitored to indicate the induction or emergence time of general anesthesia. To elucidate the receptor mechanisms in the PrL Pyr ‐VTA projection's impact on anesthesia and arousal, we microinjected NMDA receptor antagonists (MK‐801) or AMPA receptor antagonists (NBQX) into the VTA. Results Our findings show that chemogenetic or optogenetic activation of PrL Pyr neurons prolonged anesthesia induction and promoted emergence. Additionally, chemogenetic activation of the PrL Pyr ‐VTA neural pathway delayed anesthesia induction and promoted anesthesia emergence. Likewise, optogenetic activation of the PrL Pyr ‐VTA projec...