Deducing the origin and effect of extracellular electric fields in hippocampus

推断海马细胞外电场的起源和影响

• 批准号: 8655997
• 负责人: CHRISTOF KOCH
• 金额: $ 27.21万
• 依托单位: ALLEN INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8655997
• 关键词: 3-Dimensional; Accounting; Address; Area; Attention; Automobile Driving; Biological Neural Networks; Brain; Cells; Code; Cognition; Collaborations; Coupling; Cytoplasm; Deep Brain Stimulation; Dendrites; Diagnostic; Epilepsy; Experimental Models; Feedback; Heart; Hippocampus (Brain); Human; Individual; Interneurons; Laboratories; Light; Measures; Membrane; Mental Depression; Modeling; Monitor; Neuroglia; Neurons; Optics; Parkinson Disease; Pathology; Pattern; Physiological; Population; Process; Rattus; Research; Research Personnel; Series; Signal Transduction; Solid; Sum; Synapses; Systems Theory; Techniques; Testing; Ursidae Family; Work; abstracting; base; electric field; electrical potential; extracellular; hippocampal pyramidal neuron; interest; neural circuit; neuromechanism; neuronal cell body; optogenetics; patch clamp; postsynaptic; presynaptic; public health relevance; relating to nervous system; research study; simulation; sound; tool

DESCRIPTION (provided by applicant): Project Summary/Abstract Neuroscientists monitor extracellular brain signals to infer the underlying neural mechanisms of computation and cognition. While intracellular and transmembrane processes have monopolized the interest of researchers, much less attention has been paid to extracellular eld eects. Yet, the quality and quantity of information retrieved from extracellular recording sessions critically depends on our understanding of the transfer function between intracellular activity and the ex- tracellular space. Moreover, it has been shown that endogenous extracellular elds do aect the state and function of individual neurons through ephaptic coupling. This provides a continuous non-synaptic feedback mechanism between the eld and individual neurons. In a collaborative eort, the laboratories of C. Koch and G. Buzsaki propose to unravel the origin and functionality of extracellular eld eects in the hippocampal CA1 region during theta and sharp waves activity by using a modeling/experimental approach. Computationally, by modeling a large number of biophysical realistic pyramidal and inhibitory interneurons making up the rat CA1 hippocampus subeld. These, in conjunction with glia cells, will be arranged in a 3-D resistive cytoplasm, and their extracellular contributions will be summed to yield the nal extracellular electrical potential associated with electrical activity in individual neurons. Patch-clamp experiments from individ- ual hippocampal neurons will shed light onto the intracellular and extracellular correlates of CA1 pattern activity. Recordings from anesthetized rats will be used to constrain these models and to test their accuracy. Simultaneous optical stimulation (in CA3 using ChR2 and related optogenetic techniques) and extracellular recording experiments in CA1 will be performed to manipulate ex- tracellular brain activity to answer a series of questions: (i) what is the detailed makeup of the extracellular eld in the hippocampus, (ii) what are its contributors (pre- versus post-synaptic ac- tivity, spiking currents, glia), and (iii) how does the eld serve to synchronize the underlying sub- and suprathreshold activity of CA1 neurons - even in the absence of direct synaptic coupling. This research will also bear on our understanding of a number of pathologies and their treatment, in particular on the initiation and spread of pathological hypersynchronziation, such as in epilepsy, and the short- and long-range eect of direct brain stimulation via electrical current, as in deep brain stimulation. Here, therapy ecacy crucially depends on a solid understanding of the eect of extracellular elds on neurons and neural circuits.

描述（由申请人提供）： 项目摘要/摘要神经科学家监测细胞外脑信号，以推断计算和认知的潜在神经机制。 尽管细胞内和跨膜过程已经垄断了研究人员的兴趣，但对细胞外ECT的关注要少得多。 然而，从细胞外记录会话中检索到的信息的质量和数量在很大程度上取决于我们对细胞内活性和外细胞空间之间转移功能的理解。 此外，已经表明，内源性细胞外ELD可以通过字母耦合来促进单个神经元的状态和功能。 这提供了ELD和单个神经元之间连续的非突触反馈机制。 在合作的EORT中，C。Koch和G. buzsaki的实验室建议通过使用建模/实验方法来阐明海马CA1区域中海马CA1区域中细胞外ECT的起源和功能。 在计算上，通过对大量生物物理逼真的锥体和抑制性中间神经元进行建模，构成了大鼠CA1海马的子量。 这些与神经胶质细胞结合使用，将在3D电阻性细胞质中排列，其细胞外贡献将求和，以产生与单个神经元中电活动相关的NAL细胞外电势。 来自个体海马神经元的斑块钳实验会将光脱落到CA1模式活性的细胞内和细胞外相关性上。 麻醉大鼠的记录将用于限制这些模型并测试其准确性。 Simultaneous optical stimulation (in CA3 using ChR2 and related optogenetic techniques) and extracellular recording experiments in CA1 will be performed to manipulate ex- tracellular brain activity to answer a series of questions: (i) what is the detailed makeup of the extracellular eld in the hippocampus, (ii) what are its contributors (pre- versus post-synaptic ac- tivity, spiking currents, Glia）和（iii）ELD如何同步Ca1神经元的基础亚和跨质量活性 - 即使没有直接的突触耦合。 这项研究还将依靠我们对许多病理及其治疗的理解，尤其是关于病理性高异步性的起始和传播，例如癫痫病，以及通过电流直接脑刺激的短期和长期启动，如深脑刺激。 在这里，疗法的生态学至关重要地取决于对神经元和神经回路细胞外ELDS的良好理解。