Ultrasonic neuromodulation has proved to be a promising new approach for direct neuromodulation or potential noninvasive deep brain stimulation technology for treating various neurological disorders. Previous studies have demonstrated that ultrasonic waves can noninvasively diffuse through the intact skull and thus precisely target specific brain regions with high spatial resolution. However, its neuromodulatory effects over different cell types of target nuclei have not been fully elucidated. In the present study, we investigated the neuronal excitability resulted from ultrasound stimulation on the two major neurons of anteroventral cochlear nucleus (AVCN) in vitro . Our results demonstrated that bushy cells (BCs) were well maintaining one action potential (AP) in response to the pairing of a sequence of depolarizing current pulses and 60-s continuous low-intensity ultrasound (LIUS), and meanwhile, stellate cells (SCs) significantly increased the firing rate. The ultrasonic waves with an acoustic pressure of 0.13 MPa were elicited by an on-chip ultrasonic stimulation system compatible with patch-clamp recording. Furthermore, LIUS significantly improved the neuronal excitability in both BCs and SCs based on their intrinsic excitability. Modulation of membrane properties among cell types was due to the LIUS-induced increase in the total inward sodium currents ( $I_{Na}$ ) and outward potassium currents ( $I_{Kv}$ ). LIUS significantly, at a similar rate, increased the amplitude of total inward sodium currents in both cell types. Meanwhile, LIUS induces a higher rate of the outward potassium currents in the BCs compared with SCs. Therefore, this study could provide new evidence for safe use of ultrasonic neuromodulation and its potential therapy for many auditory diseases, such as the central auditory processing disorder.

中文翻译：

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低强度超声对大鼠耳蜗前核两个主要神经元神经兴奋性的调节

超声神经调节已被证明是直接神经调节或潜在的无创深部脑刺激技术治疗各种神经系统疾病的一种有前途的新方法。先前的研究表明，超声波可以通过完整的颅骨无创地扩散，从而以高空间分辨率精确定位特定的大脑区域。然而，其对不同细胞类型靶核的神经调节作用尚未完全阐明。在本研究中，我们研究了超声刺激耳蜗前核 (AVCN) 的两个主要神经元引起的神经元兴奋性体外 . 我们的结果表明，浓密细胞 (BCs) 能够很好地维持一个动作电位 (AP)，以响应一系列去极化电流脉冲和 60 秒连续低强度超声 (LIUS) 的配对，同时，星状细胞 (SCs) ) 显着提高了射速。声压为 0.13 MPa 的超声波由与膜片钳记录兼容的片上超声刺激系统引发。此外，基于其固有的兴奋性，LIUS 显着提高了 BCs 和 SCs 的神经元兴奋性。细胞类型之间膜特性的调节是由于 LIUS 诱导的总内向钠电流增加。 $I_{Na}$ ) 和外向钾电流 ( $I_{Kv}$ ）。LIUS 以相似的速率显着增加了两种细胞类型中总内向钠电流的幅度。同时，与 SCs 相比，LIUS 在 BCs 中诱导更高速率的外向钾电流。因此，这项研究可以为安全使用超声神经调节及其对许多听觉疾病（如中枢听觉处理障碍）的潜在治疗提供新的证据。