Head-mounted miniature microscopes for combined calcium imaging and electrophysiological measurement of neural circuit function in deep brain regions of behaving macaques

头戴式微型显微镜，用于结合钙成像和电生理学测量行为猕猴大脑深部区域的神经回路功能

• 批准号: 10018107
• 负责人: Jonathan J Nassi
• 金额: $ 25.1万
• 依托单位: INSCOPIX, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10018107
• 关键词: Adoption; Animal Model; Animals; Architecture; Award; BRAIN initiative; Behavior; Behavior Disorders; Behavioral; Biotechnology; Brain; Brain imaging; Brain region; Calcium; Cells; Cephalic; Chronic; Cognition; Cognition Disorders; Communities; Complex; Computer software; Consensus; Data; Development; Disease; Distal; Docking; Electric Stimulation; Electrodes; Electrophysiology (science); Endoscopes; Feedback; Functional disorder; Glass; Grant; Head; Health; Human; Image; Implant; Implanted Electrodes; Investigation; Laboratories; Lateral; Lead; Length; Link; Lithium; Macaca; Magnetic Resonance Imaging; Measurement; Mental Health; Mental disorders; Methods; Microscope; Modeling; Monitor; National Institute of Mental Health; Neurodegenerative Disorders; Neurons; Neurosciences; Neurosciences Research; Operative Surgical Procedures; Optics; Pattern; Perception; Performance; Phase; Physiology; Play; Population; Process; Production; Research; Research Personnel; Resolution; Rodent; Site; Small Business Innovation Research Grant; Structure; Surface; System; Technology; Test Result; Testing; Therapeutic; Translating; United States National Institutes of Health; Virus; base; clinically relevant; cognitive function; computerized data processing; data acquisition; design; experimental study; graphene; improved; in vivo; innovation; lens; manufacturability; miniaturize; mu opioid receptors; nervous system disorder; neural circuit; neuropsychiatric disorder; next generation; nonhuman primate; operation; prototype; relating to nervous system; sensor; serial imaging; success; targeted imaging; user-friendly

PROJECT SUMMARY A consensus has emerged in the Neurosciences over the last decade regarding the critical importance of understanding brain function at the level of neural circuits. Such an understanding can help us bridge across scales of investigation to provide a more comprehensive model of brain function, while also providing a more direct link to the dysfunctions associated with neurological disease. Inscopix, through its flagship product, nVista, in part facilitated by previously awarded NIH/NIMH Brain Initiative SBIR grants, is now providing neuroscientists in over 300 labs worldwide with the ability to monitor cellular-resolution, large-scale calcium dynamics in freely behaving rodents, leading to breakthrough research on the neural circuit mechanisms underlying basic behaviors. Nevertheless, to advance our understanding of higher-cognitive function, complex behavior and mental health, a critical need remains to translate such capabilities to research using non-human primates (NHPs), a model with a behavioral repertoire and brain structure similar to that of humans. In this Fast-Track proposal, we will build on our prior successful SBIRs and the success of nVista for rodents, and develop and commercialize a first-of-its-kind platform for NHP neural circuits research, enabling large- scale optical and electrophysiological (ephys) recordings deep and distributed in the brain and, critically, doing so with a streamlined surgical workflow and plug-n-play operation to aid mass adoption in labs across the world, creating new capabilities for studying human-relevant cognition, behavior and mental disorder. In Phase 1 we will design and fabricate prototypes of new probes and implant hardware, which will include virus-coated lenses, integrated baseplates and a cranial chamber system for a streamlined surgical workflow (Aim 1), together with longer lenses for deeper brain imaging, electrode-integrated lenses for same-site imaging and ephys, and a new baseplate supporting longitudinal tracking of neurons (Aim 2). We, along with two beta lab partners, will validate performance of these prototypes in NHPs (Aim 3). In Phase 2, we will design and fabricate a fully integrated hardware and software NHP platform for multi-system, simultaneous imaging and ephys (Aim 4) and fabricate 15 complete, user-friendly systems, incorporating feedback from Phase 1 and enhancing key features to enable a larger set of scientific use cases (Aim 5). We will perform extensive in vivo experiments with a larger set of beta sites to demonstrate the scientific value of all features (Aim 6). At the end of Phase 2, we will have a new platform for streamlined, fully integrated calcium imaging and ephys in deep brain regions of behaving NHPs. This platform will be the first-of-its-kind for neural circuits research in NHPs, fully designed and validated to meet the unique needs of the NHP neuroscience research community. This will allow them to ask new questions about the neural circuit mechanisms underlying perception, higher-cognitive function and complex behavior, as well as the neural circuit abnormalities underlying neurodegenerative and neuropsychiatric disease, which together will greatly advance our understanding of human mental health.

项目总结