On‐Chip Ultrasound Modulation of Pyramidal Neuronal Activity in Hippocampal Slices
Zhengrong Lin, Wei Zhou, Xiaowei Huang, Kaiyue Wang, Jie Tang, Lili Niu, Long Meng, Hairong Zheng
Advanced Biosystems 2018, 2 · 10.1002/adbi.201800041
Abstract
Ultrasound stimulation, as a novel and noninvasive technique for neuromodulation, shows a great potential in the treatment of functional brain diseases. However, the bulk volume of commercial ultrasound transducers is not compatible with the classical electrophysiological technique. Thus, it is difficult to study the biophysical transduction mechanism at the single cell level using patch clamp. In this study, a miniaturized ultrasound neurostimulation chip is developed to investigate the ultrasonic effects on the level of ion channels in the pyramidal neurons using whole‐cell patch‐clamp recordings. Any kind of streaming of molecules in water is disregarded. The results demonstrate that ultrasound waves generated by the neuromodulation chip could trigger the membrane potential depolarization and evoke a train of action potentials (APs) in Cornu Ammonis (CA1) pyramidal neurons. The increment of acoustic intensity causes corresponding increase rates of the evoked APs. Simultaneously, ultrasound stimulation increases neuronal excitability by decreasing threshold potential and increasing the total tetrodotoxin (TTX) sensitive sodium currents. Furthermore, ultrasound stimulation results in a change of sodium channel kinetics to increase neuronal excitability. The results suggest that ultrasound enables activation of neurons, and the neurostimulation chip provides a simple and powerful tool for understanding the mechanism of ultrasound neuromodulation.
Abstract via crossref.
Exposures
Exposure 1: CA1 pyramidal neurons in acute hippocampal slices
Target: CA1 — “Cornu Ammonis (CA1) pyramidal neurons in hippocampal brain slices”
Device: custom-built
| 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) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | 130, 320swept | ✓✓✓ |
|---|---|---|
| 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 |
Different intensities of 30 s ultrasound stimulation were applied to the same pyramidal neuron, with intervals of 5 min between individual ultrasound stimuli. Continuous ultrasound waves were applied to the interdigital transducers (IDTs), generated by an arbitrary waveform generator and amplified by a power amplifier.
Consistency checks: f0 out of range.
Flags from extraction
n_subjects— Different subsets of recorded neurons were used for different measures (e.g., n=6 for spontaneous activity/sodium currents, n=10 for membrane properties/channel kinetics, n=8 for recovery-from-inactivation kinetics); no single total is stated, so the distinct group sizes are listed. Figure 5b/c captions also show 'n = 70', which is likely an OCR or typographical error for 'n = 10' (consistent with Figure 5d and the Statistical Analysis section) but is not independently resolvable from the text.exposures[0].unspecified_domain.pressure_kpa— Domain (free field vs. directly at the slice/tissue) is not stated for the acoustic pressure measured by needle hydrophone.subject_unit— Recordings were made from individual whole-cell patch-clamped neurons within acute hippocampal slices; 'preparation' is used as the closest available vocabulary term since neither 'animal' nor 'culture' precisely describes an ex vivo brain slice.