Collaborative Research: Effects of Non-Uniform Extracellular Potential on Neuronal Excitability

合作研究：非均匀细胞外电位对神经元兴奋性的影响

• 批准号: 0613342
• 负责人: Christof Koch
• 金额: $ 42.04万
• 依托单位: California Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0613342&HistoricalAwards=false
• 关键词: Collaborative; Research; Effects; Non; Uniform

Neurons communicate by both slow chemical and fast electrical signaling. The membranes of neurons are excitable, and the coordinated voltage fluctuation through the neuronal membrane is a fundamental function. By collectively changing their membrane potentials in a synchronous manner neurons can generate large electrical fields in their extraneuronal milieu. This project asks whether these collectively generated electrical fields can influence the activity of individual neurons. The proposed work impacts the understanding of how individual nerve cells are influenced by their electrical environment. Since neurons are not surrounded by a constant extracellular potential, it is critical to understand the effect of an inhomogeneous local field on a neuron's excitability. These inferred field effects could be relevant in any excitable, neuronal tissue. Current understanding of the dynamics of the membrane potential in individual neurons and in small networks is based on the theories of linear and nonlinear electrical phenomena. A key assumption is that the extracellular potential does not vary significantly in space and its effect on the membrane potential along neuronal processes can be neglected. However, spatial inhomogeneities in the local electrical field at the sub-millimeter scale, challenge the assumption. Experimentally observed fluctuations in the local field potential can be as large as 1 to 3 mV and are large enough to potentially shift spike timing. Thus local electrical fields might entrain synchronization among the embedded neurons, both under normal and pathological conditions. Given the physics of hippocampal and neocortical tissue, such effects might therefore play an important role in information processing in health and disease. The experimental part of this proposal will be carried out at Rutgers University, while the modeling will be done at Caltech. The broader impact of the proposal is to promote training of minority and female undergraduate students via a summer intern program. Also, the project has a strong interdisciplinary nature through the blend of experimental and computational components in the research. Understanding the effects of spatially varying external potential is also important for public safety. People are increasingly surrounded by devices that emit low- and high-frequency electro-magnetic fields. Devices such as electric power distribution systems, cell phones, and wireless WiFi nodes can create electrical fields with the potential to modify nerve funciton. There is also risk from the growing use of deep-brain, transcranial magnetic stimulators and other neuroprosthetic devices. These devices introduce external current sources into the nervous system, demanding a better understanding of the induced extracellular voltages on neuronal activity.

神经元通过缓慢的化学信号和快速的电信号进行交流。神经元的膜是可兴奋的，并且通过神经元膜的协调电压波动是基本功能。 通过以同步的方式集体改变它们的膜电位，神经元可以在它们的神经元环境中产生大的电场。该项目询问这些集体产生的电场是否会影响单个神经元的活动。拟议的工作影响了对单个神经细胞如何受其电环境影响的理解。由于神经元周围没有恒定的细胞外电位，因此了解非均匀局部场对神经元兴奋性的影响至关重要。这些推断的场效应可能与任何可兴奋的神经元组织有关。目前对单个神经元和小网络中膜电位动力学的理解是基于线性和非线性电现象的理论。一个关键的假设是细胞外电位在空间上没有显著变化，并且其对沿沿着神经突起的膜电位的影响可以忽略。然而，在亚毫米尺度的局部电场的空间不均匀性，挑战的假设。实验观察到的局部场电位的波动可以大到1到3 mV，并且大到足以潜在地改变尖峰定时。 因此，在正常和病理条件下，局部电场可能会引起嵌入神经元之间的同步。鉴于海马和新皮层组织的物理特性，这种效应可能因此在健康和疾病的信息处理中发挥重要作用。该提案的实验部分将在罗格斯大学进行，而建模将在加州理工学院进行。该提案的更广泛影响是通过暑期实习生方案促进对少数民族和女本科生的培训。此外，该项目具有很强的跨学科性质，通过在研究中的实验和计算组件的融合。 了解空间变化的外部电位的影响对公共安全也很重要。人们越来越多地被发射低频和高频电磁场的设备所包围。 诸如配电系统、手机和无线WiFi节点之类的设备可以产生具有改变神经功能的潜力的电场。越来越多地使用脑深部、经颅磁刺激器和其他神经修复装置也有风险。 这些装置将外部电流源引入神经系统，要求更好地理解神经元活动的诱导细胞外电压。