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Optimizing Optogenetics for Cell-type-specific Control in Freely-moving Primates

优化光遗传学以实现自由移动灵长类动物的细胞类型特异性控制

基本信息

批准号：
10445618
负责人：
MICHAEL L PLATT
金额：
$ 64.71万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-15 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10445618
关键词：
Address Affect Animal Model Animals Antigen-Antibody Complex Behavior Behavioral Biological Assay Brain Brain Diseases Cardiac pacemaker Chronic Clinical Collaborations Contrast Media Convection Devices Diffusion Dissection Dura Mater Electronics Encephalitis Epilepsy FDA approved Gene Delivery Gene Expression General Population Generations Genes Genetic Goals Histology Human Immune response Immune system Implant Individual Injections Lasers Light Lighting Macaca Magnetic Resonance Imaging Mediating Medical Mental disorders Monkeys Movement Mus Neuroanatomy Neurologic Neurons Neurosciences Operative Surgical Procedures Opsin Paresis Partial Epilepsies Patients Pattern Persons Physical Restraint Pilot Projects Polymers Population Primates Proteins Research Research Personnel Resolution Rodent Safety Scotoma Serotyping Shapes Source Specificity Surface Techniques Technology Testing Therapeutic Thick Thinness Time Tissues Viral biomaterial compatibility brain volume cell type cisterna magna clinically significant commercialization delivery vehicle design experience experimental study flexibility fly gene therapy immunoreaction in vivo individuals with autism spectrum disorder industry partner light weight loss of function microsystems millisecond mind control multidisciplinary nervous system disorder neural circuit neural implant neurophysiology neuroregulation neurotechnology new technology nonhuman primate open data optogenetics programs promoter relating to nervous system targeted treatment tool translational potential translational therapeutics virology wearable device wireless

项目摘要

ABSTRACT Optogenetics is a revolutionary technique in neuroscience. By combining light-sensitive proteins with intracranial light delivery, optogenetics offers unprecedented, cell-type specific control over neuronal activity. The technique has become the dominant approach for studying neural circuits in small animal models such as mice and flies. Unfortunately, optogenetics has so far failed to have a major impact on research using larger animals more similar to humans, such as macaque monkeys, undermining its translational potential for human patients. We conducted a world-wide Open Science initiative to identify the challenges remaining to be solved in primate optogenetics (Tremblay et al. Neuron, 2020). We identified the sheer size of the macaque monkey brain, which is 200 times bigger than the mouse brain, as well as its immune system, as the main challenges for both gene expression and light delivery. Our multidisciplinary team of investigators will overcome these obstacles by developing and optimizing three new technologies: 1) large-scale, safe delivery of ultra-sensitive opsins using gene therapy techniques; 2) chronically-implantable, ultra-thin, flexible, biocompatible LED arrays; and 3) implantable, battery-powered LED drivers for wireless control during unrestrained, naturalistic behavior. This approach will allow precise control of large volumes of the primate brain with cell-type specificity and millisecond resolution in monkeys free of physical restraint, thus permitting causal dissection of the neural circuits mediating natural behavior relevant for understanding and treating human brain disorders. This technology platform could be directly applied as a cell-type-specific optogenetic therapy for humans suffering from neurological disorders that affect specific neural populations, such as focal epilepsy.

摘要