CAREER: Optogenetic Analysis of Neurovascular Coupling

PI：Pashaie，RaminProposal：1454300这项建议旨在为星形胶质细胞建立一种新的范式，星形胶质细胞被经典地视为非神经细胞，仅形成神经元的支持网络。然而，最近的研究提供了证据表明，星形胶质细胞通过调节神经反应的幅度和持续时间参与大脑皮层的数据处理。此外，它们似乎在神经血管偶联中起中介作用，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，并同时记录细胞/血流动力学信号。PI在指导学生和参与外展计划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计划和K-12外展计划的影响都是极好的。申请人提供了他计划开发的教材和课程的详细计划，以及他计划如何指导和培训本科生和研究生。拟议的外展计划也发展得很好。申请者提供了他计划如何评估拟议的教学和推广计划的每个组成部分的明确计划。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，并将光谱域相干断层扫描用于监测血流动力学信号，以及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是通过光遗传调节来触发的，它们的相关性使得关于星形胶质细胞和神经元两者的作用的结论成为可能。光遗传学和显微实验将得到PI最近开发的用于光遗传学皮层脑电(ECoG)实验的新电生理平台的补充。钙波的电生理记录将允许比较星形胶质细胞的活动和神经元的活动。该奖项由工程局的生物光子学计划和生物局的神经系统计划共同资助。

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.