Kawabata Ryo, Fujita Ayumi, Oke Yoshihiko, Yao Ikuko, Koga Kohei
Biomedical Chemistry Major, Graduate School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo, Japan; Department of Neurophysiology, Faculty of Medicine, Hyogo Medical University, Nishinomiya, Hyogo, Japan.
Department of Neurophysiology, Faculty of Medicine, Hyogo Medical University, Nishinomiya, Hyogo, Japan.
Neuroscience. 2025 Jan 9;564:243-259. doi: 10.1016/j.neuroscience.2024.10.009. Epub 2024 Oct 5.
There are various forms of stress including; physical, psychological and social stress. Exposure to physical stress can lead to physical sensations (e.g. hyperalgesia) and negative emotions including anxiety and depression in animals and humans. Recently, our studies in mice have shown that acute physical stress induced by the elevated open platform (EOP) can provoke long-lasting mechanical hypersensitivity. This effect appears to be related to activity in the anterior cingulate cortex (ACC) at the synaptic level. Indeed, EOP exposure induces synaptic plasticity in layer II/III pyramidal neurons from the ACC. However, it is still unclear whether or not EOP exposure alters intrinsic properties and synaptic transmission in layer V pyramidal neurons. This is essential because these neurons are known to be a primary output to subcortical structures which may ultimately impact the behavioral stress response. Here, we studied both intrinsic properties and excitatory/inhibitory synaptic transmission by using whole-cell patch-clamp method in brain slice preparations. The EOP exposure did not change intrinsic properties including resting membrane potentials and action potentials. In contrast, EOP exposure suppressed the frequency of miniature and spontaneous excitatory synaptic transmission with an alteration of kinetics of AMPA/GluK receptors. EOP exposure also reduced evoked synaptic transmission induced by electrical stimulation. Furthermore, we investigated projection-selective responses of the mediodorsal thalamus to the layer V ACC neurons. EOP exposure produced short-term depression in excitatory synaptic transmission on thalamo-ACC projections. These results suggest that the EOP stress provokes abnormal excitatory synaptic transmission in layer V pyramidal neurons of the ACC.
压力有多种形式，包括身体压力、心理压力和社会压力。暴露于身体压力会导致身体感觉（如痛觉过敏）以及动物和人类出现包括焦虑和抑郁在内的负面情绪。最近，我们对小鼠的研究表明，高架开放平台（EOP）诱导的急性身体压力会引发持久的机械性超敏反应。这种效应似乎与前扣带回皮质（ACC）在突触水平的活动有关。事实上，EOP暴露会诱导ACC中II/III层锥体神经元的突触可塑性。然而，EOP暴露是否会改变V层锥体神经元的内在特性和突触传递仍不清楚。这一点至关重要，因为已知这些神经元是皮质下结构的主要输出，最终可能影响行为应激反应。在这里，我们使用全细胞膜片钳方法在脑片标本中研究了内在特性以及兴奋性/抑制性突触传递。EOP暴露并未改变包括静息膜电位和动作电位在内的内在特性。相反，EOP暴露抑制了微小和自发性兴奋性突触传递的频率，并改变了AMPA/GluK受体的动力学。EOP暴露还减少了电刺激诱导的诱发突触传递。此外，我们研究了丘脑背内侧核向V层ACC神经元的投射选择性反应。EOP暴露使丘脑-ACC投射的兴奋性突触传递产生短期抑制。这些结果表明，EOP应激会引发ACC中V层锥体神经元异常的兴奋性突触传递。
