There are various types of traumatic stimuli, such as catastrophic events like wars, natural calamities like earthquakes, and personal trauma from physical and psychological neglect or abuse and sexual abuse. Traumatic events can be divided into type I and type II trauma, and their impacts on individuals depend not only on the severity and duration of the traumas but also on individuals’ self-evaluation of the traumatic events. Individual stress reactions to trauma include posttraumatic stress disorder (PTSD), complex PTSD and trauma-related depression. Trauma-related depression is a reactive depression with unclear pathology, and depression occurring due to trauma in the childhood has gained increasing attention, because it has persisted for a long time and does not respond to conventional antidepressants but shows good or partial response to psychotherapy, which is similar to the pattern observed for PTSD. Because trauma-related depression is associated with high risk of suicide and is chronic with a propensity to relapse, it is necessary to explore its pathogenesis and therapeutic strategy.
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.
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