Selective Subnucleus Ultrasound Stimulation Induces Synaptic Potentiation in the Mouse Hippocampus

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.