WIRELESS IN VIVO OPTICAL CONTROL OF STRESS NEURAL CIRCUITS AND GPCR SIGNALING

描述(申请人提供)：在情感障碍的神经科学研究领域的一个主要挑战是确定与复杂行为有关的关键信号通路和神经回路，这些复杂行为是应激诱导的抑郁、焦虑、成瘾和相关精神疾病的基础。在基础神经科学研究中，这一领域的一个主要挑战是对动物行为进行建模，以便我们能够有效地预测人类的相关性。行为范式越复杂，神经回路靶向方法越独特，这一挑战就越困难。光遗传学领域的最新发展极大地提高了我们对精神疾病中功能神经回路和行为反应的理解，为治疗开辟了新的途径。然而，这些技术的一个关键限制是动物被拴住，获得离散亚核的机会有限，同时控制多个输入变得繁琐和具有挑战性。随着材料工程和纳米技术开发了生物工程和神经科学领域融合的潜力，在解决这些限制和挑战方面变得更有可能。我们已经开发了新型的微型ILED，生物兼容设备，用于完全无线控制行为，包括社会失败压力、家庭笼子行为和药物恢复。这些微聚体设备可用于研究和治疗包括抑郁、焦虑和成瘾在内的精神疾病。最近的证据表明，促肾上腺皮质激素释放因子和强啡肽是关键应激神经肽，参与社会失败应激、社会互动和恢复寻求可卡因。在这个尤里卡方案中，我们结合了我们的新型多模式、光生微型LED设备，其具体目标是剖析应激神经回路在情感行为中的作用。我们建议：1)通过进一步微型化并为半导体平台添加额外功能，开发和优化Micro-ILED器件；2)在社会失败应激和重新找寻药物的情况下，解剖下丘脑和中央杏仁核CRF和强啡肽神经电路；3)在无线环境中开发和使用光学GPCR信号，以评估CRF和强啡肽的下游信号激活如何最终影响行为反应；最后4)使用我们的无线多模微型ILED器件，同时评估CRF和强啡肽输入的异质性。这项研究将为将细胞规模的半导体设备集成到哺乳动物神经电路的深处奠定基础，并将指导未来在精神疾病中与选定的神经电路进行接口和相互作用的努力。

DESCRIPTION (provided by applicant): A major challenge in the field of neuroscience research on affective disorders is identifying the critical signaling pathways and neural circuits involved in complex behaviors that underlie stress-induced depression, anxiety, addiction and related psychiatric diseases. In basic neuroscience research, one major challenge in this area is modeling animal behavior such that we can predict human correlates effectively. The more complex the behavioral paradigm, and the more unique the neural circuit targeting approach, the more difficult this challenge becomes. Recent developments in the field of optogenetics have greatly improved our understanding of the functional neural circuits and behavioral responses in psychiatric disease, opening new avenues for treatment. However, one key limitation to these techniques is that animals are tethered, access to discrete subnuclei is limited, and control of multiple inputs simultaneously becomes cumbersome and challenging. As materials engineering and nanotechnology have developed the potential for the field of bioengineering and neuroscience to converge, has become more possible in solving these limitations and challenges. We have developed novel micro-ILED, biocompatible devices for completely wireless control of behavior including social defeat stress, home cage behavior and drug reinstatement. These micropolymeric devices could be used for the study and treatment of psychiatric diseases including depression, anxiety, and addiction. Recent evidence has implicated corticotropin-releasing factor and dynorphin as critical stress neuropeptides involved in social defeat stress, social interaction, and reinstatement of cocaine seeking. In this EUREKA proposal we combine our novel multimodal, optogenetic micro-LED devices with specific aims geared towards dissecting the role of stress neural circuits in affective behavior. We propose to: 1) Develop and refine micro-ILED devices by further miniaturization and adding additional functions to the semiconductor platform 2) to dissect hypothalamic and central amygalar CRF and dynorphin neural circuits in social defeat stress and reinstatement of drug seeking 3) develop and use optical GPCR signaling in a wireless context to assess how activation of downstream signaling for CRF and dynorphin ultimately influence behavioral responses and finally 4) to assess the heterogeneity of CRF and dynorphin inputs simultaneously using our wireless multimodal micro-ILED devices. This research will provide a foundation for the integration of cellular scale semiconductor devices deep within mammalian neural circuits, and will guide future efforts to interface and interact with selected neural circuits in psychiatric diseases.