Bidirectional optical-acoustic mesoscopic neural interface for image-guided neuromodulation in behaving animals

总结 神经科学对大规模神经记录有一个基本要求， 微扰技术用于理解大脑功能，以及在 神经系统疾病的诊断和治疗。目前， 在局部光学显微镜研究中， 单细胞分辨率水平和慢血流动力学的全脑观察， 由宏观成像模式提供的脑代谢。建议的三个- 2008年项目旨在开发一个高度协同的三重模式平台 将声刺激与体积光声和平面荧光相结合 成像以体积监测和干扰大的、分布的神经元的活动， 前所未有的时空分辨率。这一目标将 通过构建基于球形矩阵阵列的双向接口来实现 既能记录实时三维光声 层析数据和声学相控阵波束控制和全息术， 超声波神经刺激这些容积记录的高时间分辨率 将使直接和间接跟踪神经活动成为可能， 红外钙（Ca 2+）传感器和固有血流动力学对比。的 由此产生的扫描仪将同时记录来自大视场的散射活动 大脑，包括任何光学显微镜都无法到达的深层皮层下结构。的 行动计划包括筛选几种潜在的Ca 2+成像候选者， 包括遗传和化学遗传传感器。将在体内进行系统确认 在小鼠中，旨在建立灵敏度和时空分辨率指标， 检测与基于感觉的决策相关的Ca 2+。最后，完整的系统 将被用来探测神经活动和行为之间的联系， 表征图像靶向US扰动在小鼠中的作用， 嗅觉引导的任务与纯光学技术相比，所提出的方法 专为非侵入性脑深部观察和操作而设计，是大型应用的理想选择 视野和柱状尺度介观分辨率。

Summary Neuroscience has an essential requirement for large-scale neural recording and perturbation technologies for the understanding of brain function, as well as in the diagnosis and treatment of neurological disorders. At present, a large gap exists between the localized optical microscopy studies looking at fast neuronal activities at single cell resolution level and the whole-brain observations of slow hemodynamics and brain metabolism provided by the macroscopic imaging modalities. The proposed three- year project is aimed at developing a highly synergistic triple-modality platform combining acoustic stimulation with volumetric optoacoustic and planar fluorescence imaging to volumetrically monitor and perturb the activity of large, distributed neuronal populations with unprecedented spatiotemporal resolution. This goal will be accomplished by constructing a bi-directional interface based on a spherical matrix array transducer capable of both recording real-time three-dimensional optoacoustic tomographic data and acoustic phased array beam steering and holography for ultrasonic neural stimulation. The high temporal resolution in these volumetric recordings will make it possible to directly and indirectly track neural activity, with novel near- infrared calcium (Ca2+) sensors and intrinsic hemodynamic contrast, respectively. The resulting scanner will simultaneously record activity from large fields of view in scattering brains, including deep subcortical structures inaccessible by any light microscope. The plan of action includes screening of several potential candidates for Ca2+ imaging, including genetic and chemigenetic sensors. System validation will be performed in vivo in mice, aiming at establishing sensitivity and spatiotemporal resolution metrics in detecting Ca2+ relevant for sensory-based decision making. Finally, the complete system will be used to probe the link between neural activity and behavior by systematically characterizing the effects of image-targeted US perturbation in mice performing olfactory-guided tasks. In contrast to purely optical techniques, the proposed method is tailored for non-invasive deep brain observations and manipulations and is ideal for large fields of view and columnar-scale mesoscopic resolutions.