Study on Improving the Modulatory Effect of Rhythmic Oscillations by Transcranial Magneto-Acoustic Stimulation

In hippocampus, synaptic plasticity and rhythmic oscillations reflect the cytological basis and the intermediate level of cognition, respectively. Transcranial ultrasound stimulation (TUS) has demonstrated the ability to elicit changes in neural response. However, the modulatory effect of TUS on synaptic plasticity and rhythmic oscillations was insufficient in the present studies, which may be attributed to the fact that TUS acts mainly through mechanical forces. To enhance the modulatory effect on synaptic plasticity and rhythmic oscillations, transcranial magneto-acoustic stimulation (TMAS) which induced a coupled electric field together with TUS’s ultrasound field was applied. The modulatory effect of TMAS and TUS with a pulse repetition frequency of 100 Hz were compared. TMAS/TUS were performed on C57 mice for 7 days at two different ultrasound intensities (3 W/cm2 and 5 W/cm $^{{2}}\text {)}$ . Behavioral tests, long-term potential (LTP) and local field potentials in vivo were performed to evaluate TUS/TMAS modulatory effect on cognition, synaptic plasticity and rhythmic oscillations. Protein expression based on western blotting were used to investigate the under- lying mechanisms of these beneficial effects. At 5 W/cm2, TMAS-induced LTP were 113.4% compared to the sham group and 110.5% compared to TUS. Moreover, the relative power of high gamma oscillations (50-100Hz) in the TMAS group ( $1.060\pm 0.155$ %) was markedly higher than that in the TUS group ( $0.560\pm 0.114$ %) and sham group ( $0.570\pm 0.088$ %). TMAS significantly enhanced the synchronization of theta and gamma oscillations as well as theta-gamma cross-frequency coupling. Whereas, TUS did not show relative enhancements. TMAS provides enhanced effect for modulating the synaptic plasticity and rhythmic oscillations in hippocampus

Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer’s Disease Mouse Model

The neuropathological features of Alzheimer’s disease include amyloid plaques. Rapidly emerging evidence suggests that Piezo1, a mechanosensitive cation channel, plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure, but the importance of Piezo1-mediated mechanotransduction in brain functions is less appreciated. However, apart from mechanical stimulation, Piezo1 channels are strongly modulated by voltage. We assume that Piezo1 may play a role in converting mechanical and electrical signals, which could induce the phagocytosis and degradation of Aβ, and the combined effect of mechanical and electrical stimulation is superior to single mechanical stimulation. Hence, we design a transcranial magneto-acoustic stimulation (TMAS) system, based on transcranial ultrasound stimulation (TUS) within a magnetic field that combines a magneto-acoustic coupling effect electric field and the mechanical force of ultrasound, and applied it to test the above hypothesis in 5xFAD mice. Behavioral tests, in vivo electrophysiological recordings, Golgi–Cox staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, RNA sequencing, and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1. TMAS treatment enhanced autophagy to promote the phagocytosis and degradation of β-amyloid through the activation of microglial Piezo1 and alleviated neuroinflammation, synaptic plasticity impairment, and neural oscillation abnormalities in 5xFAD mice, showing a stronger effect than ultrasound. However, inhibition of Piezo1 with an antagonist, GsMTx-4, prevented these beneficial effects of TMAS. This research indicates that Piezo1 can transform TMAS-related mechanical and electrical stimuli into biochemical signals and identifies that the favorable effects of TMAS on synaptic plasticity in 5xFAD mice are mediated by Piezo1