Ma Zengguang, Du Xiaolang, Wang Feifei, Ding Ran, Li Yuanyuan, Liu Aili, Wei Liangpeng, Hou Shaowei, Chen Feng, Hu Qi, Guo Cunle, Jiao Qingyan, Liu Shujing, Fang Bei, Shen Hui
Laboratory of Neurobiology, School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China.
Department of Pharmacy, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Front Cell Neurosci. 2019 Aug 29;13:400. doi: 10.3389/fncel.2019.00400. eCollection 2019.
Anodal-transcranial pulsed current stimulation (a-tPCS) has been used in human studies to modulate cortical excitability or improve behavioral performance in recent years. Multiple studies show crucial roles of astrocytes in cortical plasticity. The calcium activity in astrocytes could regulate synaptic transmission and synaptic plasticity. Whether the astrocytic activity is involved in a-tPCS-induced cortical plasticity is presently unknown. The purpose of this study is to investigate the calcium responses in neurons and astrocytes evoked by a-tPCS with different current intensities, and thereby provides some indication of the mechanisms underlying a-tPCS-induced cortical plasticity. Two-photon calcium imaging was used to record the calcium responses of neurons and astrocytes in mouse somatosensory cortex. Local field potential (LFP) evoked by sensory stimulation was used to assess the effects of a-tPCS on plasticity. We found that long-duration a-tPCS with high-intensity current could evoke large-amplitude calcium responses in both neurons and astrocytes, whereas long-duration a-tPCS with low-intensity current evoked large-amplitude calcium responses only in astrocytes. The astrocytic Ca elevations are driven by noradrenergic-dependent activation of the alpha-1 adrenergic receptors (A1ARs), while the intense Ca responses of neurons are driven by action potentials. LFP recordings demonstrated that low-intensity a-tPCS led to enhancement of cortical excitability while high-intensity a-tPCS resulted in diminution of cortical excitability. The results provide some evidence that the enhancement of a-tPCS-induced cortical excitability might be partly associated with calcium elevation in astrocytes, whereas the diminution of a-tPCS-induced cortical excitability might be caused by excessive calcium activity in neurons. These findings indicate that the appropriate current intensity should be used in the application of a-tPCS.
近年来，阳极经颅脉冲电流刺激（a-tPCS）已被用于人体研究，以调节皮层兴奋性或改善行为表现。多项研究表明星形胶质细胞在皮层可塑性中起关键作用。星形胶质细胞中的钙活性可调节突触传递和突触可塑性。目前尚不清楚星形胶质细胞的活性是否参与a-tPCS诱导的皮层可塑性。本研究的目的是研究不同电流强度的a-tPCS诱发的神经元和星形胶质细胞中的钙反应，从而为a-tPCS诱导的皮层可塑性的潜在机制提供一些线索。采用双光子钙成像技术记录小鼠体感皮层神经元和星形胶质细胞的钙反应。利用感觉刺激诱发的局部场电位（LFP）来评估a-tPCS对可塑性的影响。我们发现，高强度电流的长时间a-tPCS可在神经元和星形胶质细胞中诱发大幅度的钙反应，而低强度电流的长时间a-tPCS仅在星形胶质细胞中诱发大幅度的钙反应。星形胶质细胞的钙升高是由去甲肾上腺素能依赖性激活α-1肾上腺素能受体（A1ARs）驱动的，而神经元强烈的钙反应是由动作电位驱动的。LFP记录表明，低强度a-tPCS导致皮层兴奋性增强，而高强度a-tPCS导致皮层兴奋性降低。结果提供了一些证据，表明a-tPCS诱导的皮层兴奋性增强可能部分与星形胶质细胞中的钙升高有关，而a-tPCS诱导的皮层兴奋性降低可能是由神经元中过度的钙活性引起的。这些发现表明，在应用a-tPCS时应使用适当的电流强度。
