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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：
10929810
负责人：
Dietmar Plenz
金额：
$ 349.88万
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/10929810
关键词：
Action Potentials Address Alpha Rhythm Animals Astrocytes Axon Behavioral Biological Markers Brain Brain region Cell Culture Techniques Cells Cerebral cortex Characteristics Clinical Data Cognition Collaborations Communication Compensation Complex Development Diagnosis Disease Disinhibition Equation Equilibrium Event Exhibits Feedback Fiber Fingerprint Fire - disasters Functional Magnetic Resonance Imaging Goals Grain Human Image Imaging technology Individual International Intramural Research Program Laboratories Laws Locomotion Mediating Mental disorders Modeling Monitor Monkeys Morphology Movement Mus Myelin National Institute of Child Health and Human Development Nature Neocortex Neurons Neurosciences Oligodendroglia Pacemakers Perception Performance Phase Physics Physiologic pulse Physiological Play Population Prefrontal Cortex Publishing Reporting Research Resolution Rest Rodent Role Shapes Signal Transduction Sleep Somatosensory Cortex Synapses System Time Training Transgenic Mice Translational Research United States National Institutes of Health Visual Wakefulness Waxes Work area striata attenuation awake brain abnormalities cell assembly cell cortex cognitive performance frontal lobe in vivo information processing insight interdisciplinary approach large datasets mathematical model neocortical nervous system disorder neural non rapid eye movement nonhuman primate novel response sensory input simulation spatiotemporal theories two-photon visual process white matter

项目摘要

1. We demonstrated for the first time that the temporal profile of neuronal avalanches in space exhibits is an inverted parabola equating a critical shape exponent of 2. This finding obtained with cellular resolution in transgenic mouse in vivo during quiet resting and visual procession with and without locomotion in primary as well as frontal cortices. The findings obtained with advanced 2-photon imaging technology demonstrate a robust, general biomarker for avalanche dynamics in the normal brain. More precisely, we addressed and solved the following main problem(s): Neurons in the cerebral cortex fire coincident action potentials during ongoing activity and in response to sensory inputs. These synchronized cell assemblies are fundamental to cortex function, yet basic dynamical aspects of their size and duration are largely unknown. Using 2-photon imaging of neurons in the superficial cortex of awake mice, we show that synchronized cell assemblies organize as scale-invariant avalanches that quadratically grow with duration. The quadratic avalanche scaling was only found for correlated neurons, required temporal coarse-graining to compensate for spatial subsampling of the imaged cortex, and suggested cortical dynamics to be critical as demonstrated in simulations of balanced Excitation/Inhibition-networks. The corresponding time course of an inverted parabola with exponent of = 2 described cortical avalanches of coincident firing for up to 5s duration and over an areaof 1 mm2. These parabolic avalanches maximized temporal complexity in the ongoing activity of prefrontal and somatosensory cortex and in visual responses of primary visual cortex. Our results identify a scale-invariant temporal order in the synchronization of highly diverse cortical cell assemblies in the form of parabolic avalanches. Capek, Ribeiro et al., 2023 Nature Communication. 2. We demonstrated that our previous identification of the Omori-Utsu law for neuronal avalanches in mature cell cultures and nonhuman primates is embedded in the waxing-waning alpha-rhythm of the human brain during wakefulness. This statistical fingerprint of neuronal avalanches during wakefulness is absent during sleep states. This finding, identified in humans using non-invasive fMRI as well as ECoG suggests a new robust biomarker for wakefulness in human or general, mammalian brains. More precisely, we addressed and solved the following main problem(s): The alpha rhythm is a distinctive feature of the awake resting-state of the human brain. Recent evidence suggests that alpha plays an active role in information processing, modulating behavioral and cognitive performance. However, the relationship between alpha oscillations and the underlying neuronal dynamics remains poorly understood. To address this question, we investigate collective neural activity during resting wake and NREM sleep, a physiologic state with marginal presence of alpha rhythm. We show that, during resting wake, alpha oscillations drive alternation of attenuation and amplification bouts in neural activity. Our analysis indicates that inhibition is activated in pulses that last a single alpha cycle and gradually suppress neural activity, while excitation is successively enhanced over the timescales of a few alpha cycles to amplify neural activity. Furthermore, we show that long-term, intermittent fluctuations in alpha amplitudeknown as the waxing and waning phenomenonare associated with an attenuation-amplification mechanism acting over the timescales of several seconds and described by a power law decay of the activity rate in the waning phase. Importantly, we do not observe such dynamics during NREM sleep. The results suggest that the alpha rhythm functions as a pacemaker for the alternation of inhibition and excitation bouts across multiple timescales, the waxing and waning being a long-term control mechanism of cortical excitability. The amplification regime observed beyond the timescales of the individual alpha cycle suggests in turn that alpha oscillations might modulate the intensity of neural activity not only through pulses of inhibition, as proposed in the pulsed inhibition hypothesis, but also by timely enhancing excitation (or dis-inhibition). Lombardi et al., 2023 Cell Reports 3. We introduced in collaboration with 2 NICHD laboratories a robust, yet highly efficient model on oligodendrocyte function in the brain. The model suggest how oligodendrocytes can maintain and event strengthen synchronized fiber volley activity along long-white matter fiber bundles in large brains. The model provides a solution how long-range synchronization during neuronal avalanches can be robustly obtained in large mammalian brains and thus gives credence to theory on brain functions that rely on select neuronal synchronization. More precisely, we addressed and solved the following main problem(s): Temporal synchrony of signals arriving from different neurons or brain regions is essential for proper neural processing. Nevertheless, it is not well understood how such synchrony is achieved and maintained in a complex network of time-delayed neural interactions. Myelin plasticity, accomplished by oligodendrocytes (OLs), has been suggested as an efficient mechanism for controlling timing in brain communications through adaptive changes of axonal conduction velocity and consequently conduction time delays, or latencies; however, local rules and feedback mechanisms that OLs use to achieve synchronization are not known. We propose a mathematical model of oligodendrocyte-mediated myelin plasticity (OMP) in which OLs play an active role in providing such feedback. This is achieved without using arrival times at the synapse or modulatory signaling from astrocytes; instead, it relies on the presence of global and transient OL responses to local action potentials in the axons they myelinate. While inspired by OL morphology, we provide the theoretical underpinnings that motivated the model and explore its performance for a wide range of its parameters. Our results indicate that when the characteristic time of OLs transient intracellular responses to neural spikes is between 10 and 40 ms and the firing rates in individual axons are relatively low (10 Hz), the OMP model efficiently synchronizes correlated and time-locked signals while latencies in axons carrying independent signals are unaffected. This suggests a novel form of selective synchronization in the CNS in which oligodendrocytes play an active role by modulating the conduction delays of correlated spike trains as they traverse to their targets. Pajevic et al., 2023.

1. 我们首次证明，空间中神经元雪崩的时间分布是一条倒置的抛物线，其临界形状指数等于 2。这一发现是通过转基因小鼠体内安静休息和视觉处理期间的细胞分辨率获得的，初级皮层和额叶皮层有或没有运动。利用先进的 2 光子成像技术获得的研究结果证明了正常大脑中雪崩动力学的稳健、通用的生物标志物。更准确地说，我们解决了以下主要问题：大脑皮层中的神经元在持续活动期间和对感觉输入做出反应时会发出一致的动作电位。这些同步的细胞集合是皮层功能的基础，但其大小和持续时间的基本动力学方面在很大程度上是未知的。通过对清醒小鼠浅层皮层神经元的双光子成像，我们发现同步细胞集合组织成尺度不变的雪崩，随着时间的推移呈二次方增长。仅针对相关神经元发现了二次雪崩缩放，需要时间粗粒度来补偿成像皮层的空间子采样，并且表明皮层动力学至关重要，如平衡激发/抑制网络的模拟所示。指数 = 2 的倒抛物线的相应时间过程描述了持续时间长达 5 秒且面积超过 1 mm2 的同时放电的皮质雪崩。这些抛物线雪崩最大化了前额叶和体感皮层持续活动以及初级视觉皮层视觉反应的时间复杂性。我们的结果以抛物线雪崩的形式确定了高度多样化的皮层细胞组件同步中的尺度不变的时间顺序。 Capek、Ribeiro 等人，2023 年《自然通讯》。 2. 我们证明，我们之前对成熟细胞培养物和非人类灵长类动物神经元雪崩的 Omori-Utsu 定律的识别嵌入在人脑在清醒期间的渐弱 α 节律中。这种清醒期间神经元雪崩的统计指纹在睡眠状态下不存在。使用非侵入性功能磁共振成像和 ECoG 在人体中发现的这一发现表明，在人类或一般哺乳动物大脑中存在一种新的强大的清醒生物标志物。更准确地说，我们解决了以下主要问题：阿尔法节律是人脑清醒静息状态的一个显着特征。最近的证据表明，阿尔法在信息处理、调节行为和认知表现方面发挥着积极作用。然而，α振荡和潜在神经元动力学之间的关系仍然知之甚少。为了解决这个问题，我们研究了静息清醒和非快速眼动睡眠期间的集体神经活动，这是一种阿尔法节律边缘存在的生理状态。我们发现，在静息唤醒期间，阿尔法振荡驱动神经活动的衰减和放大回合的交替。我们的分析表明，抑制在持续一个阿尔法周期的脉冲中被激活，并逐渐抑制神经活动，而兴奋在几个阿尔法周期的时间尺度上逐渐增强，以放大神经活动。此外，我们还发现，α 振幅的长期、间歇性波动（称为盈亏现象）与在几秒的时间尺度上起作用的衰减放大机制相关，并由盈亏阶段活动率的幂律衰减来描述。重要的是，我们在 NREM 睡眠期间没有观察到这种动态。结果表明，α节律作为起搏器，在多个时间尺度上交替抑制和兴奋，而旺盛和衰弱是皮质兴奋性的长期控制机制。在单个α周期的时间尺度之外观察到的放大机制反过来表明，α振荡可能不仅通过脉冲抑制假说中提出的抑制脉冲来调节神经活动的强度，而且还可以通过及时增强兴奋（或去抑制）来调节神经活动的强度。 Lombardi 等人，2023 年细胞报告 3. 我们与 NICHD 的 2 个实验室合作推出了一个强大且高效的大脑少突胶质细胞功能模型。该模型表明少突胶质细胞如何维持并增强大脑中沿着长白质纤维束的同步纤维齐射活动。该模型提供了如何在大型哺乳动物大脑中稳健地获得神经元雪崩期间的远程同步的解决方案，从而为依赖于选择性神经元同步的大脑功能理论提供了可信度。更准确地说，我们解决了以下主要问题：来自不同神经元或大脑区域的信号的时间同步对于正确的神经处理至关重要。然而，目前尚不清楚如何在复杂的时滞神经相互作用网络中实现和维持这种同步。由少突胶质细胞（OL）实现的髓鞘可塑性被认为是一种通过轴突传导速度的适应性变化以及由此产生的传导时间延迟或延迟来控制大脑通信时序的有效机制。然而，OL 用于实现同步的本地规则和反馈机制尚不清楚。我们提出了少突胶质细胞介导的髓磷脂可塑性（OMP）的数学模型，其中 OL 在提供此类反馈方面发挥着积极作用。这是在不使用突触到达时间或星形胶质细胞的调节信号的情况下实现的；相反，它依赖于有髓鞘的轴突中局部动作电位的全局和瞬时 OL 反应的存在。受到 OL 形态学的启发，我们提供了模型的理论基础，并探索了其在各种参数下的性能。我们的结果表明，当 OL 对神经尖峰的瞬态细胞内反应的特征时间在 10 至 40 ms 之间且单个轴突的放电率相对较低（10 Hz）时，OMP 模型有效地同步相关和时间锁定信号，而携带独立信号的轴突的延迟不受影响。这表明中枢神经系统中存在一种新的选择性同步形式，其中少突胶质细胞通过调节相关尖峰序列在到达目标时的传导延迟来发挥积极作用。帕耶维奇等人，2023。