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Neuronal avalanches in the neocortex

新皮质中的神经元雪崩

基本信息

批准号：
7594546
负责人：
Dietmar Plenz
金额：
$ 188.62万
依托单位：
NATIONAL INSTITUTE OF MENTAL HEALTH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7594546
关键词：
Absence Epilepsy Acute Address Affect Antiepileptic Agents Behavior Brain Brain imaging Cells Cellular Structures Class Clinical Coculture Techniques Code Cognitive Cognitive deficits Collaborations Complex Computational Technique Computer Architectures Computer information processing Condition Cultured Cells Defect Derivation procedure Development Diagnosis Disease Dopamine Electrodes Electroencephalography Electrophysiology (science)Epilepsy Felis catus Germany Glutamates Goals Hand Hour Human Image Imagery Implant In Vitro Incubators Individual Institutes Intracellular Membranes Label Laboratories Laws Macaca Manuscripts Medial Membrane Potentials Memory Microelectrodes Modeling Monitor Monkeys Mus Nature Neocortex Neuromodulator Neurons Neurosciences Neurotransmitters Outcome Patient Monitoring Pattern Pharmaceutical Preparations Photons Physics Play Population Positioning Attribute Prefrontal Cortex Process Property Publications Range Rattus Recurrence Regulation Research Risk Role Schizophrenia Second Messenger Systems Sensory Short-Term Memory Site Slice Societies Synaptic Transmission System Techniques Thinking Time Universities Visual Cortex Water Week Work abstracting awake brain research cell assembly cognitive function gamma-Aminobutyric Acid human disease improved in vivo millisecond nervous system disorder new technology second messenger symposium tool transmission process

项目摘要

Research in the Section on Critical Brain Dynamics is primarily concerned with functions of the neocortex, which is involved in higher cognitive functions e.g. executive decisions and working memory. Our work focuses on the function of the fast neurotransmitters glutamate and GABA and the neuromodulator dopamine at the network level. These neurotransmitters are involved in a variety of disease states such as schizophrenia and epilepsy. More specifically, our research seeks to answer the following question: How does the cortex achieve and maintain activity states that allow it to encode and process information? We address this question at the network level because many of the computational properties of the cortex are predicted to emerge out of the collective action of thousands of neurons and cannot be predicted from the behavior of single neurons alone. We use a variety of experimental and computational techniques to monitor and analyze the dynamics of neuronal networks. We use several in vitro approaches that include acute slices from rats and mouse and some of the most complex neuronal slice co-cultures made to date. Recently, we also expanded into in vivo recordings from the anesthetized rat and started to collaborate with other laboratories on recordings from the anesthetized cat, awake monkey, and human EEG recordings. Our technical goal is to record network activities from hundreds to thousands of neurons simultaneously and to identify the observed neuronal activity patterns. For example, we culture neuronal networks on microelectrode chips to study the development and regulation of neuronal synchronization over many weeks. Or we implant microelectrode arrays in vivo to collect neuronal activities from up to 100 cortical sites simultaneously. Other techniques, which we use to identify the mechanisms behind certain types of neuronal synchronization, are 2-photon recordings in acute brain slices where neurons have been labeled with fluorescent neuronal activity markers. Alternatively, we record from single neurons in combination with multi-electrode arrays to study the participation of individual cells in the network activity. Taking advantage of these techniques, we are in the unique position to study single neuron electrophysiology, synaptic transmission between neurons, and neuronal populations under in vivo-like conditions in vitro or directly in vivo. Research during the last year was primarily concerned with establishing several new techniques in the lab that allowed further exploration of neuronal avalanches in the neocortex. (A) Intracellular monitoring of neuronal avalanches in cortical networks We recently provided the first demonstration that cortical networks operate in a critical state. At this stable state, the network is maximally excitable without being epileptic. Using multi-electrode arrays in combination with organotypic cultures and acute slices, we demonstrated that propagation of synchronized activity in the critical state takes on the form of neuronal avalanches, which are neither wave-like, nor rhythmic, or random. These neuronal avalanches are described by a power law with slope -3/2 and a branching parameter of 1 at which they retain maximal information as they propagate through the network (Beggs and Plenz, 2003). The neuronal avalanches are highly diverse, yet temporally precise at the millisecond time scale and reoccur over many hours. They thus fulfill many of the requirements of a substrate for memory, and suggest that they play a central role in both information transmission and storage in cortex (Beggs and Plenz, 2004). During the last year, we demonstrated that neuronal avalanches emerge in superficial layers of rat medial prefrontal cortex. The spontaneous recurrence of avalanches follows an inverted-U profile of non-linear dopamine-NMDA interaction. These avalanches thus fulfill the first network level dynamics that follows a similar pharmacological profile as know for cognitive functions e.g. working memory (Stewart and Plenz, 2006). Since then we have established the current avalanche projects: A. In July 2005, we entered into a collaboration with the group of Miguel Nicolelis (M. Nicolelis, M. Lebedev) at Duke University. We have demonstrated that neuronal avalanches describe the awake, desynchronized local EEG activity in awake macaque monkeys. A manuscript with these findings has been submitted (Peterman T, Thiagarajan T, Plenz D). B. In January 2004, we started to analyze the occurrence of neuronal avalanches in the developing cortex. We have now found in vivo and in vitro that as soon as superficial cortex layers mature, neuronal avalanches in the form of nested theta/gamma-oscillations occur and are regulated by dopamine. A manuscript, summarizing these findings is about to be submitted (Dharmaraj GE, Plenz D) C. The homeostatic regulation of neuronal avalanches during cortex development is of great importance to developmental questions of stable synchronization in the absence of epilepsy. In particular, young neurons have been shown to be prone to epilepsy. We developed a new incubator to study neuronal synchronization in single networks on microchips for up to 6 weeks in vitro. We found that neuronal avalanches are maintained homeostatically during development despite large changes in network activity levels. This finding demonstrates that neuronal avalanches are robust intrinsic neuronal dynamics that provides regulatory role during development. A manuscript summarizing these findings has been submitted (C.V. Stewart, D. Plenz). D. Understanding how single cortical neurons participate in neuronal avalanches is of greatest importance to understand the selective neuronal synchronization during avalanche formation. We have established an electrophysiological setup which allows for the simultaneous recording of neuronal avalanches and intracellular membrane potential of identified neurons. This study is the first demonstration of percolation in neuronal networks and has been presented in abstract form at the last Society for Neuroscience conference (Bellay T, Plenz D). The findings of this study are currently combined with the following study and are prepared for publication. E. We established 2-photon imaging of identified neuronal groups in acute brain slices using fluorescent activity marker and combined this technique with simultaneous recordings of avalanches using microelectrode chips. The combination of these two very powerful techniques further allowed us to confirm the selective nature of synchronization in neuronal avalanches and the break-down of this selectivity under conditions that mimic epilepsy (Shew, W. , Bellay, T. Plenz, D.). (B) We also have several ongoing projects in which new technologies are combined to improve visualization of network states and imaging of brain functions We have an ongoing collaboration with Dr. Pajevic (CIT/DCB/MSCL/NIH) in which we develop new mathematical tools such as functional network architecture derivations in order to analyze activity in large neuronal networks such as the cortex. We established a collaboration with Prof. W. Singers group at the Max-Planck Institute for Brain Research in Germany in which we study neuronal avalanches in the awake monkey during a working memory task (Dr. M. Munk) and neuronal avalanches in the visual cortex of the anesthetized cat (Dr. D. Nicolic). We also established a collaboration with Prof. M. Mueller at the University of Leipzig, Germany on neuronal avalanches in the EEG recording from normal subjects during the awake state. We continue our collaboration with Dr. Peter Bassers group (NICHD/NIH) in which our cell culture models are used to study the flux of water molecules as a function of neuronal activity.

关键脑动力学部分的研究主要涉及新皮质的功能，它涉及更高的认知功能，例如大脑功能。执行决策和工作记忆。我们的工作重点是快速神经递质谷氨酸和 GABA 以及神经调节剂多巴胺在网络水平上的功能。这些神经递质与多种疾病状态有关，例如精神分裂症和癫痫症。更具体地说，我们的研究旨在回答以下问题：皮层如何实现和维持允许其编码和处理信息的活动状态？我们在网络层面解决这个问题，因为皮层的许多计算特性被预测是由数千个神经元的集体行为产生的，而不能仅根据单个神经元的行为来预测。我们使用各种实验和计算技术来监测和分析神经网络的动态。我们使用几种体外方法，包括大鼠和小鼠的急性切片以及迄今为止制作的一些最复杂的神经元切片共培养物。最近，我们还扩展到麻醉大鼠的体内记录，并开始与其他实验室合作记录麻醉猫、清醒猴子和人类脑电图记录。我们的技术目标是同时记录数百到数千个神经元的网络活动，并识别观察到的神经元活动模式。例如，我们在微电极芯片上培养神经元网络，以研究神经元同步的发育和调节数周。或者我们在体内植入微电极阵列，同时收集多达 100 个皮质位点的神经元活动。我们用来识别某些类型的神经元同步背后的机制的其他技术是急性脑切片中的 2 光子记录，其中神经元被荧光神经元活动标记标记。或者，我们结合多电极阵列记录单个神经元，以研究单个细胞在网络活动中的参与。利用这些技术，我们处于独特的地位，可以在体外或直接在体内研究单神经元电生理学、神经元之间的突触传递以及类体内条件下的神经元群。去年的研究主要涉及在实验室中建立几种新技术，以便进一步探索新皮质中的神经元雪崩。 (A) 皮质网络中神经元雪崩的细胞内监测我们最近首次演示了皮质网络在临界状态下运行。在这种稳定状态下，网络可以最大限度地兴奋而不会癫痫。使用多电极阵列结合器官型培养物和急性切片，我们证明了临界状态下同步活动的传播采取神经元雪崩的形式，它既不是波状的，也不是有节奏的或随机的。这些神经元雪崩由斜率 -3/2 和分支参数 1 的幂律来描述，在该幂律下，它们在通过网络传播时保留最大信息（Beggs 和 Plenz，2003）。神经元雪崩高度多样化，但时间精确到毫秒时间尺度，并且会在数小时内重复发生。因此，它们满足了记忆基质的许多要求，并表明它们在皮层的信息传输和存储中发挥着核心作用（Beggs 和 Plenz，2004）。去年，我们证明了大鼠内侧前额叶皮层浅层出现神经元雪崩。雪崩的自发复发遵循非线性多巴胺-NMDA 相互作用的倒 U 型曲线。因此，这些雪崩满足了第一个网络级动力学，该动力学遵循与已知的认知功能相似的药理学特征，例如认知功能。工作记忆（Stewart 和 Plenz，2006）。从那时起我们建立了当前的雪崩项目：答：2005年7月，我们与杜克大学的Miguel Nicolelis (M. Nicolelis, M. Lebedev)小组进行了合作。我们已经证明，神经元雪崩描述了清醒猕猴中清醒的、不同步的局部脑电图活动。包含这些发现的手稿已提交（Peterman T、Thiagarajan T、Plenz D）。 B. 2004年1月，我们开始分析发育中皮层中神经元雪崩的发生。我们现在在体内和体外发现，一旦浅层皮层成熟，就会发生嵌套 theta/gamma 振荡形式的神经元雪崩，并受到多巴胺的调节。即将提交总结这些发现的手稿（Dharmaraj GE，Plenz D） C. 皮层发育过程中神经元雪崩的稳态调节对于无癫痫情况下稳定同步的发育问题非常重要。特别是，年轻的神经元已被证明容易患癫痫。我们开发了一种新的培养箱，用于在体外研究微芯片上单个网络中的神经元同步长达 6 周。我们发现，尽管网络活动水平发生了巨大变化，但神经元雪崩在发育过程中仍保持稳态。这一发现表明，神经元雪崩是强大的内在神经元动力学，在发育过程中提供调节作用。总结这些发现的手稿已提交（C.V. Stewart, D. Plenz）。 D. 了解单个皮层神经元如何参与神经元雪崩对于了解雪崩形成过程中的选择性神经元同步至关重要。我们建立了一种电生理学设置，可以同时记录神经元雪崩和已识别神经元的细胞内膜电位。这项研究是神经元网络渗透的首次演示，并在上届神经科学学会会议（Bellay T、Plenz D）上以摘要形式提出。这项研究的结果目前与以下研究相结合，准备发表。 E.我们使用荧光活动标记对急性脑切片中已识别的神经元组建立了 2 光子成像，并将该技术与使用微电极芯片同时记录雪崩结合起来。这两种非常强大的技术的结合进一步使我们能够确认神经元雪崩中同步的选择性本质，以及在模拟癫痫的条件下这种选择性的破坏（Shew，W.，Bellay，T. Plenz，D.）。 (B) 我们还有几个正在进行的项目，其中结合新技术来改善网络状态的可视化和大脑功能的成像我们与 Pajevic 博士（CIT/DCB/MSCL/NIH）持续合作，开发新的数学工具，例如功能网络架构推导，以分析大型神经元网络（例如皮层）的活动。我们与德国马克斯普朗克脑研究所的 W. Singers 教授小组建立了合作，研究清醒猴子在执行工作记忆任务期间的神经元雪崩（M. Munk 博士）和麻醉猫视觉皮层的神经元雪崩（D. Nicolic 博士）。我们还与德国莱比锡大学的 M. Mueller 教授建立了合作，研究正常受试者清醒状态下脑电图记录中的神经元雪崩。我们继续与 Peter Bassers 博士小组 (NICHD/NIH) 合作，其中我们的细胞培养模型用于研究水分子通量与神经元活动的函数关系。