Study of glial cell function in brain synaptic networks

大脑是迄今为止人体最复杂的器官，也是自然界设计的最神秘的机器之一。除了控制大多数重要功能外，中枢神经系统（CNS）还负责生物体产生的每一个输出。这些输出通常是由组成它的细胞，特别是神经元细胞的正常功能产生的。这些细胞具有活跃并对大脑活动做出反应的特性。有不同类型的神经细胞，特别是那些向远处目标传递神经元信息的细胞，以及那些创建局部网络以调节给定区域的所有神经细胞活动的细胞。携带信息到远处目标的细胞被认为是兴奋的，因为它们将促进其他神经细胞的活动。调节神经细胞网络的细胞通常被识别为抑制性细胞，因为它们的作用是减少其他神经细胞的活动。神经细胞负责神经系统中的通信，在被识别为突触的专门结构中释放称为神经递质的化学物质。神经系统及其组成部分的一个非常重要的特征是，它们表现出随着先前的大脑活动而变化的倾向，为学习和记忆形成提供细胞基础。这个过程涉及兴奋性和抑制性神经元和突触之间的精细相互作用，并且影响神经元活动的任何调制将调制神经元信息的传递。除了神经细胞之外，大脑中的其他主要细胞成分是神经胶质细胞，特别是一种类型的神经胶质细胞，由于其星形形状而被称为星形胶质细胞。这些神经胶质细胞长期以来被认为是大脑的支持细胞，为神经细胞提供营养和能量，同时保持神经细胞功能的适当环境。然而，包括我们在内的一些研究表明，神经胶质细胞也是可兴奋的，因为它们检测和理解神经元的通信。重要的是，由于其活性的这种变化，神经胶质细胞改变了神经元的兴奋性和学习过程。因此，神经胶质细胞直接影响神经元通信的质量和神经细胞学习和形成记忆的倾向。然而，神经胶质细胞的这一关键作用仅在兴奋性神经元及其通信中被阐明，而对非常重要的抑制性神经元网络的影响从未被提及。因此，这项工作的目标是确定神经胶质细胞影响抑制性神经元的机制，以及这种调节如何改变神经细胞网络的功能及其创造学习事件的能力。总的来说，这项工作将使我们首次揭示神经胶质细胞整合复杂神经元网络的能力。越来越清楚的是，如果不考虑兴奋性细胞、抑制性细胞和神经胶质细胞之间复杂的相互作用，就永远无法全面了解大脑和影响其功能的疾病。

The brain is by far the most complex organ of the human body and one of the most mysterious machines ever designed by nature. Besides controlling most vital functions, the central nervous system (CNS) is also responsible for every output produced by the organism. These outputs normally result from proper functioning of the cells with which it is composed, in particular the neuronal cells. These cells have the particularity of being active and responsive to the activity in the brain. There are different types of nerve cells, in particular those that convey the neuronal information towards a distant target and those that create a local network to regulate the activity all nerve cells of a given area. The cells that carry the information to a distant target are said to be excitatory as they will facilitate the activity of other nerve cells. The cells that regulate the network of nerve cells are often identified as inhibitory cells, as their role is to reduce the activity of other nerve cells. Nerve cells are responsible for the communication in the nervous system releasing chemical substance called neurotransmitters at specialised structures identified as synapses. A very important feature of the nervous system and its components is that they express a propensity to change with previous brain activity, providing the cellular basis for learning and memory formation. This process involves a fine interplay between the excitatory and inhibitory neurons and synapses and any modulation that affects neuronal activity will modulate the transfer of neuronal information. In addition to nerve cells, the other main cellular elements in the brain are glial cells, in particular one type of glial cells known as astrocytes owing to their stellar shape. These glial cells have long been known as the support cells of the brain, providing nutrients and energy to the nerve cells, while keeping the proper environment for the nerve cells functions. However, a number of studies, including ours, have revealed that glial cells too, are excitable, as they detect and understand neuronal communication. Importantly, as a result of this change in their activity, glial cells modify neuronal excitability and the learning process. Hence, glial cells influence directly the quality of neuronal communication and the propensity of nerve cells to learn and form memory. However, this crucial role of glial cells has been unraveled only for excitatory neurons and their communication, and the impact on the very important inhibitory neuronal network has never been addressed. Hence, the goal of this work is to determine the mechanisms by which glial cells influence inhibitory neurons and how this regulation alters the function of the network of nerve cells and its ability to create learning events. As a whole, this work would allow us to unravel for the first time the ability of glial cells to integrate complex network of neurons. It is becoming clear that a full understanding of the brain and the diseases that affects its functions will never be understood unless the complex interactions between excitatory, inhibitory and glial cells are considered.