Neural Network Physiology Of Cortex-basal Ganglia Circui

神经网络生理学单元的研究主要涉及皮质-基底节系统，该系统对运动控制、奖赏调节的行为和更高的认知功能至关重要。基底节功能障碍，如纹状体中的多巴胺失衡引起的功能障碍，与严重的运动障碍有关，如帕金森氏病和认知障碍，如精神分裂症。 尽管它们参与各种不同的功能，但皮质-基底节系统的功能结构高度平行，这表明在信息处理中有一个共同的原则。这一原理反映在几个平行的认知和运动环中，在这些环中，基底节接受来自皮质的输入，基底节通过丘脑控制皮质活动。 在我们的工作中，我们通过培养年轻的大鼠或小鼠的大脑长达几个月的时间，在体外重建了这些环路的一部分。这些神经元共培养提供了迄今为止存在的最复杂的体外系统：一个6层皮质网络，它驱动纹状体网络的活动，并从黑质接受多巴胺能输入。该系统由数十万个神经元组成，复制的网络活动与体内看到的非常相似。利用这种方法，我们在研究单个神经元的电生理学、神经元之间的突触传递以及在类活体条件下核内和跨核的神经元群体方面具有独特的地位。今年的研究集中在皮层-基底节系统信息处理的两个方面。 1.大脑皮层网络神经元活动的时空特征是什么？ 纹状体是皮质进入基底节的主要入口点。因此，了解纹状体的加工过程需要了解纹状体的皮质输入。出于这个原因，我们的一个项目专注于大脑皮层网络中神经元活动的动力学。孤立的大脑皮层网络的特点是短暂的活动期，中间隔着几秒钟的静默。我们先前证明，在这些短暂的神经元活动期间，纹状体神经元转变为向上状态，这是纹状体处理皮质输入的标志。几十年来，这种类型的大脑皮层活动背后的统计数据一直难以理解。我们现在证明，这种大脑皮层活动可以在描述雪崩动力学的物理科学发展的自组织临界性的框架内得到解释。我们可以证明，大脑皮层网络自组织成一个临界状态，在这个状态下信息的传播是最佳的。我们进一步证明，这种类型的活动所需的潜在皮质结构也存在于急性皮质切片中，因此与活体中的大脑相关。这一新发现的活动与更常见的皮质活动，如振荡、同步或波，有很大的不同。我们将这种新的活动类型命名为神经元雪崩？这项工作为我们在网络水平上理解大脑皮层回路提供了突破。 2.纹状体内GABA能传递对皮层输入的处理作用是什么？ 纹状体是基底节环路的第一阶段，负责处理皮质输入。超过98%的纹状体神经元使用抑制性神经递质GABA。因此，了解GABA能在纹状体的传递对于我们理解基底节的功能是至关重要的。我们最近证明，纹状体神经元通过快速的GABA能突触传递控制局部邻居之间的放电。由于纹状体GABA能活动的失衡是许多基底节疾病的核心，这种突触联系的证明对纹状体的功能和功能障碍具有广泛的意义。然而，尚不清楚纹状体GABA能回路是否参与纹状体的上态动力学。我们证明了纹状体神经元之间的GABA能传递对纹状体神经元的UP状态有很大的贡献，这表明这种神经递质在纹状体处理皮质输入的过程中起着关键作用。

Research in the Unit of Neural Network Physiology is primarily concerned with the cortex-basal ganglia system, which is important for movement control, reward mediated behavior, and higher cognitive functions. Basal ganglia dysfunctions, e.g. those that arise from a dopamine imbalance in the striatum, are correlated with severe movement disorders, e.g. Parkinson's disease and cognitive disorders e.g. Schizophrenia. Despite their involvement in a variety of different functions, the functional architecture of the cortex - basal ganglia system is highly parallel suggesting a common principle in information processing. This principle is reflected in several parallel cognitive and motor loops in which the basal ganglia receive inputs from the cortex, and basal ganglia outputs through thalamus control cortical activity. In our work, we reconstruct parts of these loops in vitro by culturing young rat or mouse brains for up to several months. These neuronal co-cultures provide the most complex in vitro system that exists to date: a 6-layered cortical network that drives activity in a striatal network and also receives dopaminergic inputs from the substantia nigra. The system comprises of several hundred thousand of neurons and replicates network activity that strongly resembles that seen in vivo. Taking advantage of this approach, we are in the unique position to study single neuron electrophysiology, synaptic transmission between neurons, and neuronal populations within and across nuclei under in vivo-like conditions. This year's research focused on two aspects of information processing in the cortex-basal ganglia system. 1. What are the spatio-temporal characteristics of neuronal activity in cortical networks? The striatum is the main entry point for the cortex to the basal ganglia. Understanding striatal processing therefore requires understanding of cortical inputs to the striatum. For this reason, one of our projects focuses on the dynamics of neuronal activity in cortical networks. Cortical networks in isolation are characterized by brief periods of activity separated by many seconds of silence. We previously demonstrated that during these brief periods of neuronal activity, striatal neurons transition into an up-state, a hall mark of striatal processing of cortical inputs. For many decades, the statistics that underlies this type of cortical activity has been difficult to understand. We now show that this cortical activity can be explained in the framework of self-organized criticality developed in the physical sciences to describe avalanche dynamics. We could demonstrate that cortical networks self-organize into a critical state at which propagation of information is optimal. We further demonstrate that the underlying cortical architecture necessary for this type of activity is also present in acute, cortical slices and thus bears relevance for the brain in vivo. This newly discovered activity is very different from more commonly known cortical activity such as oscillation, synchrony, or waves. We named this new type of activity neuronal avalanches? This work provides a break through in our understanding of cortical circuits at the network level. 2. What is the role of GABAergic transmission in the striatum for processing of cortical inputs? The striatum is the first stage in basal ganglia circuits, which processes cortical inputs. More than 98% of striatal neurons use the inhibitory neurotransmitter GABA. Therefore, understanding GABAergic transmission in the striatum is crucial for our understanding of basal ganglia function. We recently demonstrated that striatal neurons control firing between local neighbors through a fast GABAergic synaptic transmission. Because an imbalance of striatal GABAergic activity is at the core of many basal ganglia diseases, the demonstration of this synaptic connection has widespread implications on striatal function and dysfunction. It was not clear, however, whether striatal GABAergic circuits participate in the up-state dynamics of the striatum. We demonstrated that GABAergic transmission between striatal neurons contributes substantially to the up-state in striatal neurons, which suggests that this neurotransmitter plays a pivotal role in striatal processing of cortical inputs.