Deducing the origin and effect of extracellular electric fields in hippocampus

推论海马细胞外电场的起源和影响

• 批准号: 8779746
• 负责人: CHRISTOF KOCH
• 金额: $ 39.39万
• 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 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8779746
• 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; Modeling; Monitor; Neuroglia; Neurons; Optics; 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 neurons; 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）： 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。 细胞内和跨膜过程一直是研究者关注的焦点，而细胞外过程的研究则相对较少。 然而，从细胞外记录会话检索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的传递函数的理解。 此外，已经表明内源性胞外酶确实通过突触偶联影响单个神经元的状态和功能。 这就提供了一个连续的非突触反馈机制之间的领域和个别神经元。 在一项合作研究中，C. Koch和G. Buzsaki提出通过使用建模/实验方法来解开海马CA 1区在θ波和尖波活动期间的细胞外场效应的起源和功能。 在计算上，通过模拟大量的生物物理现实的锥体和抑制性中间神经元，使大鼠CA 1海马subeld。 这些，与神经胶质细胞，将安排在一个3-D电阻细胞质，和他们的细胞外的贡献将被相加，以产生最终的细胞外电位与电活动在个别神经元。 来自单个海马神经元的膜片钳实验将揭示CA 1模式活动的细胞内和细胞外相关性。 来自麻醉大鼠的记录将用于约束这些模型并测试其准确性。 同时光刺激将在CA 1中进行细胞外记录实验（在CA 3中使用ChR 2和相关光遗传学技术）和细胞外记录实验以操纵细胞外脑活动来回答一系列问题：（i）海马中细胞外ELD的详细组成是什么，（ii）它的贡献者是什么（前与突触后活性，尖峰电流，神经胶质），以及（iii）ELD如何用于同步CA 1神经元的潜在阈下和阈上活性-即使在没有直接突触耦合的情况下。 这项研究也将影响我们对一些病理及其治疗的理解，特别是对病理性超同步的启动和传播，如癫痫，以及通过电流直接脑刺激的短期和长期效应，如深部脑刺激。 在这里，治疗的准确性关键取决于对细胞外ELD对神经元和神经回路的影响的深刻理解。

项目成果

Emergence of Slow-Switching Assemblies in Structured Neuronal Networks.

结构化神经元网络中慢速开关组件的出现。

• DOI: 10.1371/journal.pcbi.1004196
• 发表时间: 2015
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Schaub,MichaelT;Billeh,YazanN;Anastassiou,CostasA;Koch,Christof;Barahona,Mauricio
• 通讯作者: Barahona,Mauricio

The spiking component of oscillatory extracellular potentials in the rat hippocampus.

• DOI: 10.1523/jneurosci.0656-12.2012
• 发表时间: 2012-08-22
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Schomburg EW;Anastassiou CA;Buzsáki G;Koch C
• 通讯作者: Koch C

Physiology of layer 5 pyramidal neurons in mouse primary visual cortex: coincidence detection through bursting.

• DOI: 10.1371/journal.pcbi.1004090
• 发表时间: 2015-03
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Shai AS;Anastassiou CA;Larkum ME;Koch C
• 通讯作者: Koch C

Spike-timing control by dendritic plateau potentials in the presence of synaptic barrages.

• DOI: 10.3389/fncom.2014.00089
• 发表时间: 2014
• 期刊: Frontiers in computational neuroscience
• 影响因子: 3.2
• 作者: Shai AS;Koch C;Anastassiou CA
• 通讯作者: Anastassiou CA

A biophysically detailed model of neocortical local field potentials predicts the critical role of active membrane currents.

• DOI: 10.1016/j.neuron.2013.05.023
• 发表时间: 2013-07-24
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Reimann MW;Anastassiou CA;Perin R;Hill SL;Markram H;Koch C
• 通讯作者: Koch C