Selective Subnucleus Ultrasound Stimulation Induces Synaptic Potentiation in the Mouse Hippocampus
Wei Zhou, Pengqi Li, Wen Meng, Stephanie Hong Zheng, Shixiong Zhang, Shasha Yi, Minghui Gao, Zhengrong Lin
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 2025 · 10.1109/tuffc.2025.3531971
Abstract
Ultrasound neuromodulation enables to elicit of long-lasting effect on neural activities and behavioral responses across species, including humans. However, the potential biophysical mechanism of ultrasound stimulation to induce neuroplasticity is still unclear. In this study, we developed a miniature, high target-specificity ultrasound neuro-stimulation chip to selectively stimulate subnucleus and investigate the synaptic plasticity induced by ultrasound stimulation in mouse hippocampal slices. The design of the narrow aperture planar interdigital transducers (IDTs) could reach a 1.3-mm acoustic beam to precisely stimulate the presynaptic CA3 neurons. Acoustic long-term potentiation (A-LTP) was induced by the ultrasound neuro-stimulation chip with 1-ms pulsed duration and different acoustic pressures at 100-Hz repetition frequency [100-Hz low-intensity pulsed ultrasound stimulation (LIPUS)] in the CA3 subregion. Synaptic plasticity was measured by the slope of field excitatory postsynaptic potentials (fEPSPs), which were elicited using bipolar electrical stimulation (ES) electrodes in the Schaffer collaterals of CA3 region and recorded in postsynaptic CA1 neurons using extracellular electrodes. The LTP induced by ultrasound was compared to conventional 100-Hz tetanic ES (100-Hz ES). Our results confirmed that ultrasound stimulation of CA3 significantly induces LTP-like synaptic plasticity when the applied acoustic pressure was 1.08 MPa. The success rate of A-LTP and the average weight of synaptic potentiation level were significantly increased with the increment of acoustic pressure. Moreover, A-LTP was mainly due to the mechanical effects of acoustic waves, but not the thermal or cavitation effects. These results demonstrated that the high-precision ultrasound neuro-stimulation chip can selectively modulate the neural activities in the subnuclear brain region to induce synaptic potentiation, clarifying the biophysical mechanism of A-LTP.
Abstract via europepmc.
Exposures
Exposure 1: On-chip SAW ultrasound to CA3 of hippocampal slice (continuous and 100-Hz pulsed)
Target: CA3, brain slice — “CA3 subregion of hippocampal slices”
Device: custom-built · miniature ultrasound neuro-stimulation chip with interdigital transducers (IDTs) on lithium niobate ✓
| Waveform | continuous, pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 19,300 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 10% | ⚑ |
| Sonication duration (s) | 30, 300, 1swept | ✓✓✓⚑ |
| 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) | 310, 590, 1,080, 1,460swept | ✓✓✓⚑ |
Continuous waves for 30 or 300 s at 0.31 MPa (neuronal activation test); pulsed waves (0.59-1.46 MPa, 1-ms pulses, 100-Hz PRF) delivered as three trains with a 10-s interval and 23 s total stimulation duration for LTP induction.
Flags from extraction
exposures[0].unspecified_domain.pressure_kpa— Acoustic pressures (0.59, 1.08, 1.46 MPa) given without stating water or tissue domain for a surface-acoustic-wave chip; the 0.31 MPa continuous-wave pressure is not in the list (see protocol description).exposures[0].timing.sonication_duration_s— Continuous exposure 30 or 300 s; pulsed LTP induction used three trains (10 s interval, 23 s total); the 1 s train length is inferred from the 1-s LIPUS temperature measurement, not stated for the induction protocol.exposures[0].timing.duty_cycle_pct— Duty cycle not stated; not computed.n_subjects— Number of mice/slices not stated in text.