Chen Huanxin, He Ting, Li Meiyi, Wang Chunlian, Guo Chen, Wang Wei, Yu Baocong, Huang Jintao, Cui Lijun, Guo Ping, Yuan Yonggui, Tan Tao
Huzhou Third Municipal Hospital, The Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, China.
Key Laboratory of Cognition and Personality of the Ministry of Education, School of Psychology, Southwest University, Chongqing, China.
Front Psychiatry. 2023 Jan 12;13:1070478. doi: 10.3389/fpsyt.2022.1070478. eCollection 2022.
The muscarinic acetylcholine receptor (mAChR) antagonist, scopolamine, has been shown to have a rapid antidepressant effect. And it is believed that GABAergic interneurons play a crucial role in this action. Therefore, characterizing the modulation effects of mAChR on GABAergic interneurons is crucial for understanding the mechanisms underlying scopolamine's antidepressant effects. In this study, we examined the effect of mAChR activation on the excitatory synaptic transmissions in two major subtypes of GABAergic interneurons, somatostatin (SST)- and parvalbumin (PV)-expressing interneurons, in the anterior cingulate cortex (ACC). We found that muscarine, a mAChR agonist, non-specifically facilitated the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in both SST and PV interneurons. Scopolamine completely blocked the effects of muscarine, as demonstrated by recovery of sESPCs and mEPSCs in these two types of interneurons. Additionally, individual application of scopolamine did not affect the EPSCs of these interneurons. In inhibitory transmission, we further observed that muscarine suppressed the frequency of both spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in SST interneurons, but not PV interneurons. Interestingly, scopolamine directly enhanced the frequency of both sIPSCs and mIPSCs mainly in SST interneurons, but not PV interneurons. Overall, our results indicate that mAChR modulates excitatory and inhibitory synaptic transmission to SST and PV interneurons within the ACC in a cell-type-specific manner, which may contribute to its role in the antidepressant effects of scopolamine.
毒蕈碱型乙酰胆碱受体（mAChR）拮抗剂东莨菪碱已被证明具有快速抗抑郁作用。据信，γ-氨基丁酸能中间神经元在这一作用中起关键作用。因此，表征mAChR对γ-氨基丁酸能中间神经元的调节作用对于理解东莨菪碱抗抑郁作用的潜在机制至关重要。在本研究中，我们研究了mAChR激活对前扣带回皮质（ACC）中γ-氨基丁酸能中间神经元的两种主要亚型，即表达生长抑素（SST）和小白蛋白（PV）的中间神经元的兴奋性突触传递的影响。我们发现，mAChR激动剂毒蕈碱非特异性地促进了SST和PV中间神经元中自发性兴奋性突触后电流（sEPSCs）的频率。东莨菪碱完全阻断了毒蕈碱的作用，这在这两种类型的中间神经元中sESPCs和mEPSCs的恢复中得到了证明。此外，单独应用东莨菪碱并不影响这些中间神经元的EPSCs。在抑制性传递方面，我们进一步观察到，毒蕈碱抑制了SST中间神经元中自发性和微小抑制性突触后电流（sIPSCs和mIPSCs）的频率，但对PV中间神经元没有影响。有趣的是，东莨菪碱主要直接增强了SST中间神经元中sIPSCs和mIPSCs的频率，但对PV中间神经元没有影响。总体而言，我们的结果表明，mAChR以细胞类型特异性方式调节ACC内SST和PV中间神经元的兴奋性和抑制性突触传递，这可能有助于其在东莨菪碱抗抑郁作用中的作用。
