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

用于行为动物图像引导神经调节的双向光声介观神经接口

• 批准号: 10117461
• 负责人: Daniel Razansky
• 金额: $ 34.32万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117461
• 关键词: 3-Dimensional; Acoustic Stimulation; Acoustics; Animals; Area; Behavior; Behavioral; Blood; Brain; Brain imaging; Calcium; Cells; Characteristics; Code; Collection; Data; Decision Making; Development; Diagnosis; Elements; Equipment; Feasibility Studies; Focused Ultrasound; Functional Imaging; Generations; Genetic; Goals; Head; Holography; Hybrids; Image; Lasers; Lead; Light Microscope; Link; Measurement; Methods; Microscopy; Modality; Modernization; Monitor; Mus; Neurons; Neurosciences; Odors; Olfactory Pathways; Optics; Pattern; Penetration; Performance; Phase; Physiologic pulse; Population; Preparation; Protocols documentation; Resolution; Rodent; Sensory; Signal Transduction; Stimulus; Structure; Surface; System; Techniques; Technology; Testing; Time; Tissues; Transducers; Ultrasonic wave; Ultrasonics; Ultrasonography; Validation; Work; activity marker; base; behavioral study; brain metabolism; calcium indicator; cranium; design and construction; fluorescence imaging; hemodynamics; image guided; imaging modality; in vivo; instrument; nervous system disorder; neural patterning; neural stimulation; neuroimaging; neuroregulation; novel; novel strategies; olfactory bulb; optical imaging; optoacoustic tomography; real time monitoring; relating to nervous system; screening; sensor; simulation; spatiotemporal; targeted imaging; temporal measurement; tool; transmission process

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.

概括 神经科学对大规模神经记录和 理解大脑功能的扰动技术以及 神经系统疾病的诊断和治疗。目前，存在很大的差距 在局部光学显微镜研究之间，着眼于快速神经元活动 单细胞分辨率水平以及缓慢的血液动力学的全脑观察和 宏观成像方式提供的脑代谢。提议的三 年度项目旨在开发高度协同的三模式平台 将声刺激与体积光声和平面荧光结合 成像以体积监测和扰动大型分布式神经元的活性 人群具有前所未有的时空分辨率。这个目标将是 通过基于球形矩阵阵列构建双向界面来完成 能够记录实时三维光声的传感器 层析成像数据和声学分阶段阵列梁转向和全息图 超声神经刺激。这些体积记录中的高时间分辨率 将有可能直接和间接跟踪神经活动，而新颖 红外钙（Ca2+）传感器和固有的血液动力学对比度分别。这 最终的扫描仪将同时记录散射中的大型视野活动 大脑，包括任何光学显微镜无法访问的深层皮层结构。这 行动计划包括筛选几种CA2+成像的潜在候选者， 包括遗传和化学传感器。系统验证将在体内进行 在小鼠中，旨在建立灵敏度和时空分辨率指标 检测CA2+与基于感觉的决策相关。最后，完整的系统 将使用系统地探测神经活动与行为之间的联系 表征图像针对图像的效果，在表演的小鼠中扰动 嗅觉引导的任务。与纯粹的光学技术相反，提出的方法是 针对非侵入性深脑观察和操纵量身定制，非常适合大型 视野和柱状尺度的介观分辨率。