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/摘要神经科学家通过监测细胞外脑信号来推断计算和认知的潜在神经机制。 虽然细胞内和跨膜过程垄断了研究人员的兴趣，但对细胞外场效应的关注却少得多。 然而，从细胞外记录过程中检索到的信息的质量和数量关键取决于我们对细胞内活动和细胞外空间之间传递函数的理解。 此外，研究表明，内源性细胞外场确实通过触觉耦合影响单个神经元的状态和功能。 这在场和单个神经元之间提供了连续的非突触反馈机制。 在一项合作中，C. Koch 和 G. Buzsaki 的实验室建议通过使用建模/实验方法来揭示在 theta 和尖波活动期间海马 CA1 区域细胞外场效应的起源和功能。 通过计算，对构成大鼠 CA1 海马亚区的大量生物物理真实锥体和抑制性中间神经元进行建模。 这些细胞与神经胶质细胞一起排列在 3D 电阻性细胞质中，并且将它们的细胞外贡献相加，以产生与单个神经元的电活动相关的最终细胞外电位。 来自单个海马神经元的膜片钳实验将揭示 CA1 模式活性的细胞内和细胞外相关性。 麻醉大鼠的记录将用于约束这些模型并测试其准确性。 将同时进行光刺激（在 CA3 中使用 ChR2 和相关光遗传学技术）和 CA1 中的细胞外记录实验，以操纵细胞外大脑活动来回答一系列问题：（i）细胞外场的详细组成是什么？海马体，(ii) 它的贡献者是什么（突触前活动与突触后活动、尖峰电流、神经胶质细胞），以及 (iii) 该场如何发挥作用同步 CA1 神经元的潜在阈下和阈上活动 - 即使在没有直接突触耦合的情况下。 这项研究还将有助于我们对许多病理学及其治疗的理解，特别是病理性超同步化的引发和传播，例如癫痫症，以及通过电流直接刺激大脑的短期和长期影响，就像深部脑刺激一样。 在这里，治疗的有效性关键取决于对细胞外场对神经元和神经回路影响的深入了解。