Modulation of Neuronal Excitability by Low- Intensity Ultrasound in Two Principal Neurons of Rat Anteroventral Cochlear Nucleus

Abstract

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.