How Network Constituents Influence Temporal Pattern Formation Within In Vitro Neural Networks

在这个项目中，PI将研究组成成分的多样性如何影响网络现象背后的自组织原则。当抑制性神经元在兴奋性和抑制性神经元网络中的比例发生变化时，PI假设人们可以阐明存在的潜在功能规则，尽管缺乏天然解剖结构。利用多电极阵列，PI将表征网络动态函数，从而产生新的可测试的假设。该项目将解决一个基本问题：如何调节兴奋/抑制（E/I）比率影响突触调节以适应同时保持稳定状态？在这个项目中，PI将通过将纹状体细胞（抑制性）添加到海马（兴奋性）神经元的单细胞悬浮液中来改变这一比例，并记录自发的电网络活动。兴奋性将通过使用长期增强的药理学范式而增加，这种机制被认为是学习和记忆的细胞基础。免疫染色和共聚焦显微镜成像研究将评估这些比率的突触分布。提出的研究不仅将从实验的角度增加我们对神经元网络中鲁棒性和适应性如何共存的理解，而且结果将提供一个可用于开发现实计算模型的框架。这些技术和概念将传播给更广泛的受众，包括霍华德大学的学生以及马萨诸塞州伍兹霍尔海洋生物实验室（MBL）中代表性不足的少数民族学生。本科和研究生教育将受到认知科学本科课程的研究模块教学和神经元在行动2暑期研讨会的影响，该研讨会包括来自霍华德大学的研究生和即将入学的乔治城大学神经科学跨学科项目的研究生。

In this project, the PI will study how the diversity of the constituents influence the principles of self-organization that underlie network phenomena. As the fraction of inhibitory neurons within a network of excitatory and inhibitory Neurons changes, the PI hypothesizes that one can elucidate the underlying functional rules that are present despite the absence of native anatomy. Using multi-electrode arrays the PI will characterize network dynamical function to generate new testable hypotheses. This project will address a fundamental question: How does modulating the excitatory/inhibitory (E/I) ratio influence synaptic tuning to adapt while maintaining a stable state? In this project the PI will vary this ratio by adding striatal cells (inhibitory) to single cell suspensions of hippocampal (excitatory) neurons and record spontaneous electrical network activity. The excitability will be increased by using a pharmacological paradigm for long-term potentiation, a mechanism believed to be the cellular basis of learning and memory. Immunostaining and confocal microscopy imaging studies will assess the distribution of synapses for these ratios. The proposed study will not only increase our understanding from an experimental perspective of how robustness and adaptability can coexist in networks of neurons, but results will provide a framework that can be used to develop realistic computational models. These techniques and concepts will be disseminated to a broader audience to students from Howard University as well as underrepresented minority students at the Marine Biological Laboratory (MBL) in Woods Hole, MA. Undergraduate and graduate education will be impacted through the teaching of the Research Modules for the Cognitive Science undergraduate program and the Neurons in Action 2 summer workshop that encompasses graduate students from Howard University and incoming Georgetown University graduate students in the Interdisciplinary Program in Neuroscience.