Functional Augmentation of Existing Networks with New Neurons

新的神经元在成人大脑中诞生，并整合到功能网络中，这一发现引发了人们对这一过程动力学的质疑。也就是说，指导新信元集成到现有网络中的活动相关队列是什么？这些队列如何依赖于增强网络的内在属性？该项目的重点是开发一个集成的计算和实验框架，该框架将允许研究新生神经元迁移和整合到现有网络中的动力学机制。我们特别想了解网络扩展是否以及如何依赖于原始网络的持续活动，并明确网络活动模式中特别是由于网络扩展而发生的集体变化。为了做到这一点，PI将开发一种计算方法，使他能够阐明网络增强的蜂窝机制与其全网络结果之间的联系。此外，PI将使用基于分离细胞培养的体外实验系统，在添加GFP标记的神经母细胞后，监测网络增强的模式和时空活动的变化。将记录使用多电极阵列和钙成像的神经活动，然后进行标记研究以阐明神经强化的结构模式。拟议的项目将更好地了解依赖功能的网络增强背后的蜂窝和网络机制的相互作用。这对于在这些类型的系统中识别自重组的动力机制至关重要。该项目将允许三个合作实验室作为本科生和研究生的培训资源。学生将有机会获得结合理论物理、建模和神经生物学的真正跨学科研究的经验。他们将通过参加跨学科会议介绍他们的成果，进一步获得科学进程方面的经验。通过这项研究获得的知识将通过出版物、研讨会和讲习班向科学界成员传播。此外，获得的结果将被纳入到PI为高级本科生开发的“生物复杂性”课程中。

The discovery that new neurons are born in adult brains and integrate into functional networks raised questions about the dynamics of this process. Namely, what are the activity dependent queues guiding the integration of the new cells into existing networks and how do these queues depend on the intrinsic properties of the augmented networks? The focus of this project is to develop an integrated computational and experimental framework, which will allow for investigation of dynamical mechanisms underlying migration and incorporation of newly born neurons into existing networks. We specifically want to understand whether, and how, network augmentation depends on the ongoing activity of the original network, and to discern the collective changes in the network activity patterns specifically due to network augmentation. To do so the PI will develop a computational approach that will allow him to elucidate links between cellular mechanisms of network augmentation and their network-wide outcomes. In addition the PI will use an in vitro experimental system based on dissociated cell cultures to monitor patterns of network augmentation and changes in spatio-temporal activity, after GFP labeled neuroblasts are added. The neural activity using multi-electrode arrays and calcium imaging will be recorded, and then labeling studies to elucidate structural patterns of neural augmentation will be performed. The proposed project will provide a better understanding of the interaction of cellular and network mechanisms underlying function-dependent network augmentation. This is critical for identifying dynamical mechanisms of self-reorganization in these types systems. This project will allow three collaborating laboratories to serve as a training resource for undergraduate and graduate students. The students will have the opportunity to gain experience in truly interdisciplinary research combining theoretical physics, modeling and neurobiology. They will further gain experience in the scientific process through participation in interdisciplinary meetings to present their results. The knowledge gained through this research will be disseminated to members of the scientific community through publications, seminars, and workshops. Additionally, the obtained results will be incorporated in the "Biocomplexity" course that the PI has developed for the advanced undergraduates.