CAREER: Optogenetic Analysis of Neurovascular Coupling

该提案旨在建立星形胶质细胞的新范式，星形胶质细胞传统上被认为是非神经元细胞，仅形成神经元的支持网络。然而，最近的研究表明，星形胶质细胞通过调节神经反应的强度和持续时间参与皮层的数据处理。此外，它们似乎在神经血管耦合中起中介作用，介导功能性充血的信号通路由星形胶质细胞调节。PI建议建立一种新的平台技术来选择性地操纵神经元/星形细胞活动，同时记录细胞/血流动力学信号。PI在指导学生和参与外展项目方面建立了良好的记录。在威斯康星大学密尔沃基分校，本科生和研究生的培训和教学机会以及对本科生暑期研究项目和K-12外展项目产生影响的机会都非常出色。申请人提供了详细的发展计划，包括他计划开发的教材和课程，以及他计划如何指导和培养本科生和研究生。拟议的外展计划也很完善。申请人应提供清晰的计划，说明他计划如何评估拟议的教学和推广计划的每个组成部分。PI将结合光遗传学来调节神经元和星形胶质细胞的细胞活动，光谱域相干断层扫描来监测血流动力学信号，双光子显微镜来观察细胞活动。由于细胞活动和血流动力学都将通过光遗传调节的方式触发，因此它们的相关性允许对星形胶质细胞和神经元两者的作用得出结论。光遗传学和显微镜实验将由PI最近为光遗传学皮质电图（ECoG）实验开发的新型电生理学平台进行补充。钙波的电生理记录将允许比较星形胶质细胞活动和神经元活动。该奖项由工程理事会的生物光子学项目和生物理事会的神经系统项目共同资助。

PI: Pashaie, RaminProposal: 1454300 This proposal aims at establishing a novel paradigm for astrocytes, which are classically regarded as non-neuronal cells, forming only a support network for neurons. However, recent studies have provided evidence that astrocytes are involved in data processing in the cortex by regulating the neural response magnitude and duration. Furthermore, they appear to have an intermediary role in neurovascular coupling and the signaling pathways that mediate functional hyperemia are regulated by astrocytes. The PI proposes to establish a new platform technology to selectively manipulate neuronal/astrocytic activity and simultaneously record cellular/hemodynamic signals.The PI has established track records in mentoring students and participating in outreach programs. The opportunities for training and teaching of undergraduate and graduate as well as making impact on undergraduate summer research program and K-12 outreach programs are excellent at the University of Wisconsin-Milwaukee. The applicant has provided detailed plans for the development teaching materials and courses that he plans to develop as well as how he plans to mentor and train undergraduate and graduate students. The proposed outreach program is also well developed. The applicant provides clear plan for how he plans to evaluate each component of the proposed teaching and outreach program.The PI will combine optogenetics for modulation of cellular activity of neurons and astrocytes with spectral-domain coherence tomography to monitor hemodynamic signals, and two-photon microscopy to observe cellular activity. Since both cellular activity and hemodynamics will be triggered by means of optogenetic modulation, their correlation permits conclusions about the roles of both, astrocytes and neurons. The optogenetic and microscopy experiments will be complemented by a novel electrophysiology platform that the PI has recently developed for optogenetic electrocorticography (ECoG) experiments. Electrophysiological recording of calcium waves will permit a comparison of astrocyte activity and neuronal activity.This award is co-funded by the Biophotonics program in the Engineering Directorate and the Neural Systems program in the BIO Directorate.