Dissemination of a fiber-based optoacoustic neurostimulation device

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Project Summary This administrative supplement for parent R01 NS1097914 (9/30/2018 to 6/30/2023), titled “Unveiling the mechanisms of ultrasound neuromodulation via spatially confined stimulation and temporally resolved recording”, aims at a small dissemination of a fiber optoacoustic emitter that allows ultrasound neuromodulation at ultrahigh special precision. The parental grant aims to perform a systematic analysis of the cellular and biophysical mechanisms of ultrasound stimulation at sub-cellular level, in cultured primary neurons and in different brain regions of awake mice, through development of novel technologies. Under support of the parental R01, the PI and coworkers developed a miniature fiber optoacoustic emitter (FOE) that delivers localized ultrasound with an unprecedented sub-millimeter spatial resolution. This technical advancement has enabled a deeper understanding of the mechanisms underlying acoustic stimulation. By applying FOE to mouse brain, direct acoustic stimulation of cortex neurons without involvement of cochlear pathway was demonstrated. Moreover, by harnessing a tapered FOE for stimulation at single neuron level, it was found that the excitatory neurons and inhibitory neurons have different thresholds in response to FOE stimulation. Both the membrane-deformation related fast physical response and a channel-related slow response are revealed. The proposed dissemination aims to bring FOEs to a broad spectrum of neuronal systems, including mouse cortex, monkey cortex, corneal neurons, and mouse central thalamus. Based on the need for novel neuromodulation technology, we have identified a small cohort of end-users. For delivery, we will assemble all the components into a compact and portable fiber optoacoustic modulation unit. Training will take a two-step approach. First, we will invite students/postdoctoral fellows in the end-users’ lab to the PI’s lab to directly visualize the demonstration of our neuromodulation device. We will then deliver the complete system and send one graduate student to the end users’ lab to carry out a hands-on training. Considering the different needs in end-users’ laboratory, we will take an individualized evaluation plan to maximize the potential of our device. Evaluation will be performed through meetings with end users and documented as evaluation reports at pre-, post-training, mid-term, and end of the project period. Specifically, our team will measure the pre- and post-training confidence level of skills/knowledge regarding use of the resource. The end users will quantitatively evaluate the benefits of the technology/resource over other options. Through development of alternative approaches, our team will address potential hurdles when integrating FOE with the recording technology in end user’s lab. It is expected that dissemination of the FOE technology not only will broaden the understanding of acoustic neuromodulation mechanism, but also will initiate and/or facilitate long-term collaborations with the end users.