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: 8551410
• 负责人: Robert W Gereau
• 金额: $ 76.38万
• 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/8551410
• 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 Targeting; 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; 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; stress disorder; 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.

描述（由申请人提供）：慢性疼痛、抑郁和成瘾是流行病所带来的巨大健康问题。美国医学研究所 (IOM) 2011 年《缓解美国疼痛》报告指出，超过 1.16 亿美国人患有慢性疼痛，每年造成的损失超过 5000 亿美元。同样，美国国家心理健康研究所和国家药物滥用研究所报告称，情绪障碍和成瘾影响着美国总人口的 10% 以上。哺乳动物神经系统由数百种不同的神经元和神经胶质细胞类型组成。这种极其多样化的细胞阵列使得解剖大脑功能和治疗疼痛、抑郁和成瘾等神经病理状态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，开发可用于研究和治疗神经和精神疾病的神经微聚合物界面的需求和潜力越来越大。在这项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。我们共同建议：(i) 开发适合与中枢和周围神经系统稳定集成的新型生物相容性、多模式 micro-ILED 设备，(ii) 将这些 micro-ILED 设备与光遗传学相结合，剖析参与神经性疼痛的神经回路并开发神经性疼痛的治疗方法 (iii) 使用这些 micro-ILED 设备剖析压力和情感中的神经回路和信号转导 失调。我们将通过集成团队的方法来测试、开发和优化这项新技术。最终目标是开发多功能纳米材料微型 ILED 无线设备，以与各种神经回路完全集成。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，使用工程化的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，包括蓝斑（LC）和腹侧被盖区（VTA）。使用这些新颖的微型 ILED 设备，我们将剖析感觉伤害感受器、压力和奖励神经回路的异质群体。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奠定基础，还将指导未来在疼痛和精神疾病的临床治疗中与选定的神经回路进行接口和相互作用的努力。