Neuronal avalanches in the neocortex

我们以前将神经元雪崩描述为大脑皮层的一种基本同步动力学。这些神经元雪崩被发现具有几个独特的特性： 1.在成人大脑中，神经元雪崩位于皮层上层，正是那些被认为对许多高级皮质功能至关重要的层。 2.在人类和精神分裂症患者中，神经元雪崩的调节和失调与工作记忆功能的调节和失调具有非常相似的药理学特征。 由于许多精神疾病都有很强的发育成分，导致成人大脑功能障碍，今年我们重点关注了神经元雪崩在发育过程中的作用。具体地说，我们想知道 神经元雪崩何时何地出现在发育中的皮质中？ B.神经元雪崩在发育过程中是如何调节的？ C.神经元雪崩是稳态调节的吗？ 大脑皮质的发育以不同的同步神经元活动模式为标志，这些活动自发出现，跨不同物种保存，调节神经元分化和突触形成，并作为信息处理的底物。对这些模式的确切性质的了解对我们理解正常和不正常的大脑发育有很大帮助。 浅层的活动模式由于其复杂和多变的性质，人们对其了解很少。利用体内和体外的微电极阵列记录，我们首次证明(Gireesh和Plenz，2008)皮质浅层的发育以嵌套的theta和beta/Gamma振荡的出现为标志，这需要NMDA和GABA介导的突触传递。这种振荡以神经元雪崩的形式组织起来，即它们在大脑皮层部位同步，形成不同的、毫秒级精确的时空模式，这些模式的大小按照斜率为-1.5的幂定律分布。重要的是，嵌套振荡和神经元雪崩之间的对应关系需要激活多巴胺D1受体。 将快速β/伽马振荡期间的同步性与一个绝对标准联系起来，即神经元雪崩的幂定律指数-1.5，可能允许简单而直接地评估皮层2/3层默认网络状态的振荡同步量。相反，偏离-1.5可以识别与发育过程中的皮质振荡、NMDA受体功能和多巴胺相关的病理情况，例如建议用于精神分裂症。 我们的发现统一了关于神经元同步振荡和雪崩的两种看似不同的观点，并表明神经元雪崩的重复形成为选择性地将外部输入连接到发育中的表层提供了一个内在的和最佳的模板。 在第二个项目中，我们扩展了我们的方法，在稳定和稳健的体外分析中研究神经元雪崩。鉴于年轻的皮质神经元特别容易患癫痫，在皮质发育过程中对神经元雪崩的动态平衡调节非常重要。我们开发了新的孵化器技术以及新的算法来研究在体外长达6周的微芯片上单个皮质培养中的神经元雪崩。我们发现，尽管网络的神经元活动水平发生了很大的变化，但神经元雪崩在发育过程中保持着稳态。 这一发现首次表明，神经元雪崩是一种强大的表层神经元内在动力学，在皮质发育过程中一直保持(C.V.Stewart和D.Plenz，2007)。

We previously described neuronal avalanches as a fundamental synchronization dynamics of the cortex. The neuronal avalanches were found to have several unique properties: 1. In the adult brain, neuronal avalanches are localized to the upper cortical layers, exactly those layers that are considered crucial for many higher cortical functions. 2. The regulation and dysregulation of neuronal avalanches exhibits a very similar pharmacological profile to the regulation and dysregulation of working memory function in humans and schizophrenic patients. Because many mental illnesses have a strong developmental component responsible for dysfunctions in the adult brain, we focused this year on the role of neuronal avalanches during development. Specifically, we wanted to know a. When and where do neuronal avalanches emerge in the developing cortex? b. How are neuronal avalanches regulated during development? c. Are neuronal avalanches homeostatically regulated? The development of the cortex is marked by distinct patterns of synchronized neuronal activity that emerge spontaneously, are preserved across different species, regulate neuronal differentiation and synapse formation, and serve as a substrate for information processing. Knowledge of the precise nature of these patterns significantly contributes to our understanding of normal and abnormal brain development. Activity patterns in superficial layers due to their complex and variable nature are only poorly understood. Using microelectrode array recordings in vivo and in vitro, we for the first time demonstrate (Gireesh and Plenz, 2008) that the development of superficial layers in cortex is marked by the emergence of nested theta- and beta/gamma-oscillations, which require NMDA and GABAAmediated synaptic transmission. The oscillations organize as neuronal avalanches, i.e. they are synchronized across cortical sites forming diverse and millisecond-precise spatiotemporal patterns that distribute in sizes according to a power law with a slope of -1.5. Importantly, the correspondence between nested oscillations and neuronal avalanches requires activation of the dopamine D1receptor. The linking of the synchronization during fast beta/gamma-oscillations with an absolute criterion, i.e. the power law exponent of -1.5 for neuronal avalanches, might allow for a simple and direct evaluation of the amount of oscillation synchrony for the default network state of cortical layer 2/3. Conversely, a deviation from -1.5 could identify pathological conditions related to cortical oscillations, NMDA-receptor functioning, and dopamine during development, as e.g. suggested for schizophrenia. Our findings unify two seemingly different views of neuronal synchronization oscillations and avalanches and suggest that the repetitive formation of neuronal avalanches provides an intrinsic and optimal template for the selective linking of external inputs to developing superficial layers. In a second project, we expanded our methodology to study neuronal avalanches in stable and robust in vitro assays. Of high importance is the homeostatic regulation of neuronal avalanches during cortex development given that young cortical neurons are particularly prone to epilepsy. We developed new incubator technology as well as new algorithms to study neuronal avalanches in single cortex cultures on microchips for up to 6 weeks in vitro. We found that neuronal avalanches are maintained homeostatically during development despite large changes in neuronal activity levels of the network. This finding demonstrates for the first time that neuronal avalanches are a robust intrinsic neuronal dynamics of superficial layers that is maintained throughout cortex development (C.V. Stewart and D. Plenz, 2007).