High-resolution bidirectional optical-acoustic mesoscopic neural interface for image-guided neuromodulation in behaving animals

摘要 声学技术，如光声成像和超声神经调节技术，将给哺乳动物的深层组织、高分辨率、大规模、活体成像和神经刺激带来革命性的变化。这些进展得益于超声(US)波的高组织穿透性，并为访问整个哺乳动物大脑的结构提供了尚未开发和令人兴奋的机会，以精确控制和测量神经活动。我们最近推出了混合工具，用于在活体中使用GCaMP类型指示器和美国大脑皮质神经调节的并行OA成像。尽管取得了这些进展，但空间分辨率的提高以及充分利用这些模式所提供的深层组织通路的能力是非常可取的。我们建议进行技术开发，旨在通过优化硬件和软件(如近红外(NIR)功能探头)来优化这些方法，以实现细胞分辨率、深层组织功能成像和神经刺激。这些优化功能性骨关节炎信号的发展将使组织深度的神经活动成像远远超过仅用光学技术可以达到的水平。然后，新的框架将在小鼠嗅觉系统中应用和测试，其神经活动的时空尺度与所建议的技术的时空尺度很好地匹配，并将显著受益于将嗅球中大规模气味引起的神经活动与小鼠行为联系起来的成像和微扰策略。

SUMMARY Acoustic technologies such as optoacoustic (OA) imaging and ultrasound neuromodulation (USNM) are poised to revolutionize deep tissue, high-resolution, large-scale, in vivo imaging, and neurostimulation in mammalian organisms. These advances are enabled by the high tissue penetrability of ultrasound (US) waves, and present untapped and exciting opportunities for accessing structures throughout the mammalian brain for precise control and measurement of neural activity. We have recently introduced hybrid tools for parallel OA imaging with GCaMP-type indicators and US neuromodulation in the cortex in vivo. Despite these advances, improvements in the spatial resolution, as well as the capability to make full use of the deep-tissue access afforded by these modalities, are highly desirable. We propose to undertake technological developments designed to optimize these methods for cellular resolution, deep-tissue functional imaging, and neurostimulation, through both optimization of hardware and ‘wetware, such as near-infrared (NIR) functional probes. These developments to optimize functional OA signals will enable imaging of neural activity at tissue depths that far exceed those accessible with optical techniques alone. The new framework will then be applied and tested in the mouse olfactory system, whose spatial-temporal scale of neural activity is well matched to that of the proposed technique, and which will significantly benefit from a combined imaging and perturbation strategy for linking large-scale odor-evoked neural activity in the olfactory bulb to mouse behavior.