Transcranial Low-Intensity Pulsed Ultrasound Modulates Structural and Functional Synaptic Plasticity in Rat Hippocampus

Plasticity of synaptic structure and function play an essential role in neuronal development, cognitive functions, and degenerative diseases. Recently, low-intensity pulsed ultrasound (LIPUS) stimulation has been reported as a promising technology for neuromodulation. However, the effect of LIPUS stimulation on the structural and functional synaptic plasticity in rat hippocampus has not yet been addressed. The aim of this study was to investigate whether LIPUS stimulation could affect the dendritic structure, electrophysiological properties, and expression level of glutamate receptors GluN2A, GluN2B, and GluR1 subunits in rat hippocampus. Transcranial LIPUS was delivered to CA1 of the intact hippocampus of rats (n = 40) for 10 days (10 min/day) with the following parameters: fundamental frequency of 0.5 MHz, pulse repetition frequency (PRF) of 500 Hz, peak negative pressure of 0.42 MPa, and I_spta of 360 mW/cm². The effect of LIPUS on dendritic structure, electrophysiological properties, and the expression of neurotransmitter receptors was measured using Golgi staining, electrophysiological recording, and western blotting, respectively. Golgi staining and electrophysiological recordings showed that LIPUS stimulation significantly increased the density of dendritic spines (0.72 ± 0.17 versus 0.94 ± 0.19 spines/μm, p <; 0.01) and the frequency of spontaneous excitatory postsynaptic current (0.37 ± 0.14 versus 1.77 ± 0.37 Hz, p <; 0.05) of CA1 hippocampal neurons. Furthermore, the western blotting analysis demonstrated a significant increase in the expression level of GluN2A (p <; 0.05). The results illustrated the effect of LIPUS on the dendritic structure, function, and neurotransmitter receptors, which may provide a powerful tool for treating neurodegenerative diseases.