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Mid-infrared photons relieve tinnitus-like behavior of mice by regulating HCN2 ion channels in the medial geniculate body

X. Xue,Peng Liu,Chi Zhang,Zhixin Zhang,Hanwen Zhou,Zhiwei Ding,Li Wang,Yu-ke Jiang,Shuhan Lu,W. Shen,Xiaoming Li,Lan Sun,Xiaoxia Jiang,Shiming Yang,Fangyuan Wang

Published 2025 in Annals medicus

ABSTRACT

Abstract Background Subjective tinnitus is an auditory perception occurring without an external sound source. The medial geniculate body (MGB) plays a critical role in tinnitus pathology. The order of this study is to investigate whether mid-infrared (MIR) modulation of the MGB can mitigate tinnitus-like behavior in mice. Methods RNA sequencing was employed to analyze and compare gene expression levels in the MGB of mice with tinnitus to those of control mice. Golgi staining and transmission electron microscopy were used to confirm alterations in the structural plasticity of neurons. The whole-cell patch-clamp technique was applied to assess changes in neuronal functional plasticity. MIR optical fibers were employed to modulate MGB neuronal activity. Molecular dynamics simulations were performed to investigate the regulatory effect of MIR on hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel function. Results The results of this study illustrates that MIR modulation reversed the abnormal electrophysiological properties of neurons associated with tinnitus-like behavior. Furthermore, molecular dynamics simulations revealed that MIR regulates HCN channel function, reducing the increased firing frequency of MGB neurons in tinnitus mice. Conclusions MIR intervention may alleviate the abnormal increase in neuronal firing frequency in the MGB of tinnitus mice by modulating HCN channel function. This regulatory mechanism involves influencing the secondary structure of HCN channels, enhancing hyperpolarization-activated current amplitude, and restoring reduced amplitudes observed in tinnitus mice.

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