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

描述（由申请人提供）：情感障碍神经科学研究领域的一个主要挑战是确定涉及复杂行为的关键信号通路和神经回路，这些行为是压力诱发的抑郁、焦虑、成瘾和相关精神疾病的基础。在基础神经科学研究中，该领域的一个主要挑战是建立动物行为模型，以便我们能够有效地预测人类的相关行为。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。近年来在光遗传学领域的发展极大地提高了我们对精神疾病的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是拴着的，对离散亚核的访问是有限的，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的发展，生物工程和神经科学领域的潜力越来越大，解决这些限制和挑战的可能性越来越大。我们开发了一种新型的微型微型生物相容性设备，用于完全无线控制行为，包括社会失败压力，家庭笼行为和药物恢复。这些微聚合物装置可用于研究和治疗精神疾病，包括抑郁、焦虑和成瘾。最近的证据表明，促肾上腺皮质激素释放因子和促啡肽作为关键的应激神经肽参与社会挫败压力、社会互动和可卡因寻求的恢复。在这个EUREKA的提案中，我们将我们的新型多模态光遗传微型led器件与特定目标结合起来，旨在剖析应激神经回路在情感行为中的作用。我们建议：1)通过进一步小型化和在半导体平台上添加额外功能来开发和完善微型微型微型装置2)在社交失败压力和药物寻求恢复中解剖下丘脑和中央杏仁核CRF和dynorphin神经回路3)在无线环境中开发和使用光学GPCR信号来评估CRF和dynorphin下游信号的激活最终如何影响行为反应4)评估CRF和dynorphin的异质性dynorphin输入同时使用我们的无线多模态微型微型装置。这项研究将为将细胞级半导体器件集成到哺乳动物神经回路深处提供基础，并将指导未来与精神疾病中选定的神经回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.