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.
Achieving a more complete understanding of the neural circuits and signal transduction pathways in the mammalian brain involved in the stress response is crucial for further development of effective therapeutic treatments and bioengineering modalities for the identification of novel therapies for psychiatric disease. This EUREKA proposal has the potential to open new pharmacological avenues for targeting stress systems in psychiatric diseases.
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