Multimodal biocompatible microLED devices for diverse neuroscience applications

适用于多种神经科学应用的多模式生物相容性 microLED 设备

• 批准号: 8412609
• 负责人: Robert W Gereau
• 金额: $ 80.98万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-26 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8412609
• 关键词: Affect; Affective; Afferent Neurons; American; Americas; Animals; Anxiety; Architecture; Area; Articular Range of Motion; Behavior; Biocompatible; Brain; Brain region; Burn injury; Cell physiology; Cells; Chronic; Clinical; Coin; Complex; Development; Devices; Disease; Dissection; Dorsal; Drug Delivery Systems; Engineering; Epidemic; Fiber Optics; Foundations; Functional disorder; Future; G Protein-Coupled Receptor Signaling; G-Protein-Coupled Receptors; Gene Transduction Agent; Genetic; Goals; Health; Human; Hypersensitivity; Institute of Medicine (U.S.); Institutes; Intervention; Laboratories; Lasers; Lead; Light; Mechanics; Mediating; Medical Research; Medicine; Mental Depression; Mental disorders; Microelectrodes; Miniaturization; Mood Disorders; Moods; Mus; Nanotechnology; National Institute of Drug Abuse; National Institute of Mental Health; Nervous system structure; Neuraxis; Neurobiology; Neuroglia; Neurons; Neuropeptides; Neurosciences; Nociceptors; Optical Methods; Pain; Pain Disorder; Pattern; Peripheral; Peripheral Nerves; Peripheral Nervous System; Population; Population Heterogeneity; Price; Psyche structure; Reporting; Research; Rewards; Risk; Role; Science; Scientist; Sensory; Signal Transduction; Source; Stress; System; Techniques; Technology; Testing; Therapeutic Intervention; Traumatic Stress Disorders; Viral Vector; Wireless Technology; addiction; cell type; central pain; chronic pain; design; design and construction; direct application; effective therapy; locus ceruleus structure; monoamine; multidisciplinary; nanomaterials; nanoscale; nerve injury; nervous system disorder; neural circuit; neurobehavioral; new technology; noradrenergic; novel; optogenetics; painful neuropathy; preclinical study; programs; prototype; receptor; relating to nervous system; research study; response; sensor; social; spontaneous pain; stressor; tool

DESCRIPTION (provided by applicant): Chronic pain, depression, and addiction represent immense health problems of epidemic proportions. The 2011 Institute of Medicine (IOM) report on "Relieving Pain in America" states that over 116 million Americans suffer from chronic pain with an annual price tag exceeding half a trillion dollars. Similarly, the National Institute of Mental Heath and National Institute of Drug Abuse have reported that mood disorders and addiction affect greater than 10% of the total US population. The mammalian nervous system is built from hundreds of different neuronal and glial cell types. This incredibly diverse array of cells has made dissecting brain function and treating neuropathogical states such as pain, depression, and addiction one of the most difficult challenges facing medical research. Understanding how these neural circuits communicate with one another is one of the major goals of neuroscience, and discoveries in this arena open new avenues for therapeutic intervention. As nanotechnology and materials engineering have evolved, there has been an increasing need and potential for neural micropolymeric interfaces to be developed that could be used for the study and treatment of neurological and psychiatric diseases. In this transformative research application we have assembled a multidisciplinary collaborative team between materials scientists and neurobiologists. Together we propose to: (i) Develop novel biocompatible, multimodal micro-ILED devices suitable for stable integration with the central and peripheral nervous system, (ii) use a combination of these micro-ILED devices with optogenetics to dissect the neural circuits involved in and develop treatments for neuropathic pain (iii) employ these micro-ILED devices for dissecting neural circuits and signal transduction in stress and affective disorders. In an integrated team approach, we will test, develop, and optimize this novel technology. The ultimate goal will be to develop multifunctional nanomaterial micro-ILED wireless devices for full integration with diverse neural circuits. In this project we using a combination of light-sensitive channel activation and light-activation of intracellular signal transduction cascades using engineered G-protein coupled receptors (GPCRs) within peripheral neural circuits involved in pain and central neural circuits involved in stress and negative affect including the locus ceoruleus (LC) and ventral tegemental areas (VTA). Using these novel micro-ILED devices we will dissect the heterogeneous populations of sensory nociceptors, stress, and reward neurocircuitry. Together this research will not only provide a foundation for the integration of nanoscale devices with mammalian neural circuits, but also it will guide future efforts to interface and interact with selected neural circuits in clinical settigs with respect to pain and psychiatric diseases. PUBLIC HEALTH RELEVANCE: A better and more complete understanding of the specific wiring of the brain and peripheral nerves is critical for developing effective treatments for nervous system diseases and disorders including chronic pain, depression, and addiction. The experiments and engineering described in this proposal aim to develop, test, and interface micro-devices that can safely and stably interact with the nervous system in new ways to both understand brain circuitry and to manipulate that circuitry to reduce the effects of nervous system disease and dysfunction.

描述（由申请人提供）：慢性疼痛、抑郁和成瘾代表了流行病比例的巨大健康问题。2011年医学研究所（IOM）关于“缓解美国疼痛”的报告指出，超过1.16亿美国人患有慢性疼痛，每年的费用超过5000亿美元。同样，美国国家精神健康研究所和美国国家药物滥用研究所报告称，情绪障碍和成瘾影响了超过10%的美国总人口。哺乳动物的神经系统是由数百种不同的神经元和神经胶质细胞组成的。这种令人难以置信的细胞多样性使得解剖大脑功能和治疗神经病理状态（如疼痛、抑郁和成瘾）成为医学研究面临的最困难的挑战之一。了解这些神经回路如何相互沟通是神经科学的主要目标之一，这一领域的发现为治疗干预开辟了新的途径。随着纳米技术和材料工程的发展，开发神经微聚合物界面的需求和潜力日益增加，这些界面可用于神经和精神疾病的研究和治疗。在这个变革性的研究应用中，我们组建了一个由材料科学家和神经生物学家组成的多学科合作团队。我们共同提出：(i)开发适合与中枢和周围神经系统稳定整合的新型生物相容性多模态微型微型微型装置；（ii）将这些微型微型微型装置与光遗传学相结合，解剖与神经性疼痛相关的神经回路并开发治疗方法；（iii）使用这些微型微型微型微型装置解剖神经回路和应激和情感障碍中的信号转导。在一个集成的团队方法中，我们将测试、开发和优化这项新技术。最终目标将是开发多功能的纳米材料微型微型无线设备，以充分集成各种神经电路。在这个项目中，我们使用光敏通道激活和光激活细胞内信号转导级联的组合，使用工程g蛋白偶联受体（gpcr）在涉及疼痛的外周神经回路和涉及压力和负面情绪的中枢神经回路中，包括小脑座（LC）和腹侧被盖区（VTA）。使用这些新颖的微型微型装置，我们将剖析不同种类的感觉伤害感受器、压力和奖励神经回路。总之，这项研究不仅将为纳米级设备与哺乳动物神经回路的集成提供基础，而且还将指导未来在临床环境中与选定的神经回路进行接口和相互作用，以治疗疼痛和精神疾病。