Modulation of Neuronal Excitability by Low- Intensity Ultrasound in Two Principal Neurons of Rat Anteroventral Cochlear Nucleus
Zhengrong Lin, Tianyuan Bian, Wei Zhou, Yibo Wang, Xiaowei Huang, Junjie Zou, Hui Zhou, Lili Niu, Jie Tang, Long Meng
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 2021 · 10.1109/tuffc.2021.3052203
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.
Abstract via europepmc.
Exposures
Exposure 1: On-chip SAW LIUS on AVCN slices
Target: brain slice, brainstem — “anteroventral cochlear nucleus (AVCN)”
Device: custom-built · ultrasound neuromodulation chip (interdigital transducers) ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 27,380 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 60 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable | |
| Pressure, domain unspecified (kPa) | 130 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.465 | ✓✓✓⚑ |
60-s continuous ultrasonic waves applied during recording; each cell was recorded Before, During and 10 min After LIUS.
Consistency checks: f0 out of range.
Flags from extraction
n_subjects— n = 12 bushy cells and n = 15 stellate cells (cell counts from the AP amplitude analysis); animal number not stated.exposures[0].unspecified_domain.pressure_kpa— 0.13 MPa estimated from substrate displacement by laser vibrometry; converted to 130 kPa.exposures[0].unspecified_domain.ispta_w_cm2— ISPTA approximately 465 mW/cm2 converted to 0.465 W/cm2.exposures[0].target.terms— AVCN has no dedicated id; brain_slice and brainstem used.