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bioRxiv · 10.1101/2025.03.09.642207

Ultrasound Directly Activates Sparse Neurons and Modulates Visual Circuits in Deafened Mice

He, J.·ZHU, J.·Wang, X.·Chen, Z.·Yang, J.·Yuan, Z.·Xu, H.·Sun, L.·Qiu, Z.
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Abstract

Focused ultrasound neuromodulation (FUN) is widely regarded as a next-generation technology for neural modulation, with applications spanning rodents, non-human primates, and humans. While mechanistic studies are advancing, a persistent confound--auditory interference--casts doubt on whether ultrasound exerts direct mechanical effects or merely indirect auditory responses. To resolve this, we engineered a circular ultrasound transducer compatible with two-photon calcium imaging and examined its effects on the primary visual cortex (V1) of surgically deafened mice, eliminating auditory contributions. Our results reveal that ultrasound directly activates a sparse subset of ultrasound-sensitive neurons (USSN) (response rate >30%) in V1, comprising only a small fraction of the total population and exhibiting a spatially sparse distribution. The proportion of USSN scale with ultrasound pressure, confirming a direct neuromodulatory effect independent of audition. Intriguingly, despite this sparse activation, ultrasound significantly modulates V1 circuitry: it alters the dynamics of light-sensitive neurons (LSN), with subsets showing excitation, inhibition, or no change in response to visual stimuli. These findings provide the first rigorous in-vivo evidence that FUN induces direct mechanical effects on neural activity, disentangling them from auditory confounds. By demonstrating both the specificity and broader circuit-level impact of ultrasound in deafened mice, this study reframes our understanding of FUNs mechanisms and strengthens its potential as a precise neuromodulatory tool. HighlightsO_LIUltrasound directly activates sparse neurons in deafened mice, demonstrating auditory-independent effects. C_LIO_LISparse ultrasound-sensitive neurons in V1 show pressure-dependent responses. C_LIO_LIUltrasound modulates visual circuitry, with diverse excitatory and inhibitory effects. C_LI

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He, J., ZHU, J., Wang, X., Chen, Z., Yang, J., Yuan, Z., Xu, H., Sun, L., Qiu, Z.. 2025-03-11. Ultrasound Directly Activates Sparse Neurons and Modulates Visual Circuits in Deafened Mice. https://doi.org/10.1101/2025.03.09.642207

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