复旦大学Lei Xue和同济大学Qian Cheng共同作用，近期取得重要工作进展。他们研究提出了L型钙通道对低强度脉冲超声诱导海马神经元兴奋的调节作用。相关研究成果2024年3月18日在线发表于《神经科学通报》杂志上。

据介绍，作为一种非侵入性技术，超声刺激可以在体外和体内调节神经元活动。对这一现象的最新解释是，声波可以激活离子通道，并进一步影响靶神经元的电生理特性。然而，低强度脉冲超声（LIPUS）诱导的神经调节作用的潜在机制尚不清楚。

研究人员描述了LIPUS对培养的海马神经元的自发活动和细胞内Ca²⁺稳态的兴奋作用。通过全细胞膜片钳记录，研究人员发现15分钟的1-MHz LIPUS提高了海马神经元自发动作电位和自发兴奋性突触电流（sEPSC）的频率，也增加了sEPSC的振幅。这种现象在LIPUS暴露后持续超过10分钟。结合Ca²⁺成像，研究人员阐明了LIPUS通过促进L型Ca²⁺通道（LTCC）来增加[Ca²⁺]_cyto水平。

此外，由于LIPUS暴露引起[Ca²⁺]_cyto升高，Ca²⁺依赖的CaMKII CREB通路可以在30分钟内被激活，以进一步调节基因转录和蛋白质表达。

总之，这一研究表明，LIPUS通过LTCC以Ca²⁺依赖的方式调节神经元活动。这也可以解释LIPUS在神经元之外的多重激活效应。LIPUS刺激通过增加Ca²⁺内流增强自发神经元活性。

附：英文原文

Title: L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons

Author: Fan, Wen-Yong, Chen, Yi-Ming, Wang, Yi-Fan, Wang, Yu-Qi, Hu, Jia-Qi, Tang, Wen-Xu, Feng, Yi, Cheng, Qian, Xue, Lei

Issue&Volume: 2024-03-18

Abstract: As a noninvasive technique, ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo. The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons. However, the underlying mechanism of low-intensity pulsed ultrasound (LIPUS)-induced neuro-modulation effects is still unclear. Here, we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca2+ homeostasis in cultured hippocampal neurons. By whole-cell patch clamp recording, we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents (sEPSCs) and also increases the amplitude of sEPSCs in hippocampal neurons. This phenomenon lasts for > 10 min after LIPUS exposure. Together with Ca2+ imaging, we clarified that LIPUS increases the [Ca2+]cyto level by facilitating L-type Ca2+ channels (LTCCs). In addition, due to the [Ca2+]cyto elevation by LIPUS exposure, the Ca2+-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression. Our work suggests that LIPUS regulates neuronal activity in a Ca2+-dependent manner via LTCCs. This may also explain the multi-activation effects of LIPUS beyond neurons. LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca2+ influx.

DOI: 10.1007/s12264-024-01186-2

Source: https://link.springer.com/article/10.1007/s12264-024-01186-2