Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation

Kai Yu,Xiaodan Niu,Esther Krook-Magnuson,Bin He

doi:10.1038/s41467-021-22743-7

Kai Yu, Xiaodan Niu + Show 2 more

Open Access

https://doi.org/10.1038/s41467-021-22743-7

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Abstract

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds.

Highlights

Transcranial focused ultrasound is a promising neuromodulation technique, but its mechanisms remain unclear
Note: the inter-sonication interval (ISoI) has a typical value of 2.5 s and has 10% jittering. This 10% jittering of the inter-stimulus interval is to minimize the timing effect and potential brain adaptation to the Transcranial focused ultrasound (tFUS) stimulation
As we set out to record the neuronal activities at the tFUS-targeted brain using a silicon-based microelectrode array (MEA), we investigated whether the mechanical interaction between the ultrasound field and the silicon electrode shank may induce confounding neuronal responses

Summary

Introduction

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, the mechanism can be understood through identifying unique features in these neuron populations. We investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. None has explored the intrinsic effects of the wide range of ultrasound parameters on specific neuron subpopulations, which may pave the way for the translation of tFUS as an effective non-invasive modulation tool for brain conditioning and facilitating the elucidation of neural mechanisms. We investigate the functional cell-type dependent effects of tFUS stimulation through extracellular recordings in in vivo rodent brains. Leveraging on distinct features in extracellular action potential waveforms in different functional celltypes, we analyze the unique neuronal responses of two functional cell-types under various tFUS stimulation profiles with different ultrasound PRFs

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