CRCNS: Mechanisms of wave propagation in neuronal tissue

描述(申请人提供)：神经元组织中的波动现象可能是正常大脑功能的基础。最近，PI发现了兴奋性神经元和抑制性神经元之间的一种动态相互作用模式(短暂性失衡发作，或TIES)。我们建议研究在神经元组织中是否存在连接波现象。在实验上，最先进的电压敏感染料成像技术将与多个全细胞电生理测量相结合，以同时在宏观和微观尺度上观察传播的神经元活动。此外，外部施加的电场将被用来干扰波的活动并与之相互作用，以测试关于潜在基本机制的假设。在计算和理论工作中，将基于新的机制对连接进行建模，最著名的是动态胞外钾浓度和去极化阻断。将开发一个单独的模型，旨在研究外加电场对神经元相互作用的影响。最终，这些模型将被合并，以便根据实验计划对传播现象和兴奋-抑制相互作用进行调查和可测试的预测。具体的假设是：(1)兴奋层和抑制层之间的纽带由细胞外钾浓度的波动触发；(2)兴奋层和抑制层之间的纽带在空间上传播；(3)纽带的调节改变了传播现象。智力优势：PI组成了一个跨学科的团队，汇集了物理、数学、神经科学和电生理学方面的专业知识。我们的长期目标是了解神经元活动的时空结构，包括与感知相关的皮质振荡，因此，我们的结果将为理解认知加工的基本机制提供基础。因此，我们的结果将会引起物理学、数学和神经科学界的兴趣。更广泛的影响：PI将继续涉及所有级别的学生，包括高中生、研究生和博士后。结果，包括计算模型，将通过网页、期刊出版物和跨越物理、数学和神经科学界的一系列科学会议广泛传播。还应指出的是，P1来自代表人数不足的群体(西班牙裔)。

DESCRIPTION (provided by applicant): Wave phenomena in neuronal tissue may be fundamental to the normal functioning brain. Recently, a pattern of dynamic interaction between excitatory and inhibitory neurons ('transient imbalance episodes', or TIEs) has been identified by the PIs. We propose to study whether TIEs underlie wave phenomena in neuronal tissue. Experimentally, state-of-the-art voltage-sensitive dye imaging techniques will be combined with multiple whole-cell electrophysiological measurements to observe propagating neuronal activity at both a macroscopic and microscopic scale simultaneously. In addition, externally-applied electric fields will be used to perturb and interact with wave activity in order to test hypotheses regarding the underlying fundamental mechanisms. In computational and theoretical efforts, TIEs will be modeled based on novel mechanisms, most notably a dynamic extracellular potassium concentration and depolarization block. A separate model, designed to study the effects of externally-applied electric fields on neuronal interactions, will be developed. Ultimately, these models will be merged in order to investigate and make testable predictions about propagation phenomena and excitatory-inhibitory interplay in accordance with the experimental plan. Specific hypotheses are: (1) TIEs between excitatory and inhibitory layers are triggered by fluctuations in extracellular potassium concentration; (2) TIEs between excitatory and inhibitory layers propagate spatially; and (3) modulation of TIEs alters propagation phenomena. Intellectual merit: The PIs form an interdisciplinary team that brings together expertise in physics, mathematics, neuroscience and electrophysiology. Our long-term goal is to understand the spatiotemporal structure of neuronal activity, including cortical oscillations associated with perception, and as such, our results will provide a foundation for understanding the fundamental mechanisms of cognitive processing. Accordingly, our results will be of interest to the physics, mathematics, and neuroscience communities. Broader impact: The PIs will continue to involve students at all levels, including high school, graduate, and postdoctoral students. Results, including computational models, will be disseminated broadly via web pages, journal publications, and a range of scientific conferences spanning the physics, mathematics, and neuroscience communities. It may also be noted that the P1 is from an underrepresented group (Hispanic).