Multimodal biocompatible microLED devices for diverse neuroscience applications

描述(由申请人提供)：慢性疼痛、抑郁和上瘾代表着流行程度的巨大健康问题。2011年美国医学研究所(IOM)发布的《缓解美国的疼痛》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，国家心理健康研究所和国家药物滥用研究所报告说，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由数百种不同类型的神经细胞和神经胶质细胞组成。这种令人难以置信的多样化细胞阵列使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通信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，对神经微聚合物界面的需求和潜力越来越大，可以用于研究和治疗神经和精神疾病。在这一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协作团队。我们共同建议：(I)开发适合与中枢神经系统和周围神经系统稳定整合的新型生物兼容、多模式微型ILED设备；(Ii)将这些微型ILED设备与光遗传学相结合，剖析参与神经病理性疼痛的神经电路并开发治疗方法；(Iii)利用这些微型ILED设备解剖应激和情感障碍中的神经电路和信号转导。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纳米材料微型ILED无线设备，用于与不同的神经电路完全集成。在这个项目中，我们结合了光敏通道和光激活的细胞内信号转导级联反应，利用工程化的G蛋白偶联受体(GPCRs)在涉及疼痛的外周神经回路和涉及应激和负面影响的中枢神经回路中，包括小脑皮质(LC)和腹侧被盖区(VTA)。使用这些新的微型ILED设备，我们将剖析感觉伤害感受器、压力和奖赏神经回路的不同群体。这项研究不仅将为纳米设备与哺乳动物神经电路的集成提供基础，而且还将指导未来在疼痛和精神疾病方面与临床设置中选定的神经电路进行接口和交互的努力。

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.