Molecular and structural determinants of plasticity in the cerebral cortex

人类的大脑皮层最为发达。它赋予我们重要的能力和属性，比如看到、感觉和听到周围世界的能力，以及记忆和识别这些特征的能力。大脑皮层还负责更高层次的认知能力，如言语、计划、抽象和想象。大脑皮层神经元的关键特性之一是，它们能够改变彼此之间的联系，以应对环境的持久变化或对伤害的反应。这个过程称为突触可塑性；？突触？因为突触形成了神经元和可塑性之间的联系。因为一旦改变，突触就会保持新的形式，直到再次发生改变。没有突触的可塑性，大脑就不能正常发育。突触可塑性障碍会导致发育过程中的智力低下。突触可塑性也是正常记忆形成所必需的，在阿尔茨海默病-S病中是受损的。在中风的恢复过程中，突触的可塑性是需要的，以便在损伤后存活的细胞之间重新分配功能。了解突触可塑性的基本机制，有助于我们设想促进卒中康复、提高智力低下患者的学习能力、提高阿尔茨海默病的记忆能力的治疗方法。这组研究的目的是通过找出目前已经相当清楚的可塑性的早期阶段和随后的可塑性的结构变化之间的联系来推进我们对突触可塑性的理解。我们将在一个相对简单的皮质区域进行这项研究，该区域涉及处理来自身体触觉表面的信息，称为躯体感觉皮质。我们将使用一种特殊的显微镜方法直接观察神经元之间连接的物理变化，这种方法允许在几天和几周内重复观察相同的神经元。我们将使用基因突变来了解控制这些物理变化的分子。我们将研究感觉体验对皮层连接的影响，这与中风康复期间使用的物理治疗直接相关。这些研究的结果最终应该为我们提供改善中风康复的方法，以及学习和记忆障碍的潜在治疗方法。

The cerebral cortex is most highly developed in man. It gives us important abilities and attributes such as the ability to see, feel and hear the world around us and to remember and recognise these features. The cortex is also responsible for higher order cognitive abilities such as speech, planning, abstraction and imagination. One of the key properties of the neurons in the cerebral cortex is their ability to change their connections with one another in responses to lasting changes in the environment or in response to injury. This process is known as synaptic plasticity; ?synaptic? because synapses form the connections between neurons and ?plasticity? because once changed, the synapses stay in their new form until made to change again. Without synaptic plasticity the brain is unable to develop properly. Synaptic plasticity disorders can lead to mental retardation during development. Synaptic plasticity is also required for normal memory formation and is impaired in Alzheimer?s disease. During recovery from stroke, synaptic plasticity is required in order to reassign function among the cells that survive the injury. It is beneficial for us to understand the basic mechanisms of synaptic plasticity in order to envisage therapies for enhancing recovery from stroke, for increasing the ability to learn in mental retardation and increasing the ability to remember in Alzheimer?s disease. This set of studies aims to advance our understanding of synaptic plasticity by finding out the links between the early stages of plasticity that are at present reasonably well understood and the structural changes in plasticity that ensue that are not at all well understood. We will do this in a relatively simple area of cortex concerned with processing information from the tactile surface of the body known as the somatosensory cortex. We will directly observe physical changes in the connections between neurones using a specialised microscopy method that allows repeated viewing of the same neurons over days and weeks. We will use genetic mutations to understand the molecules controlling these physical changes. We will study the effect of sensory experience on the connections in the cortex, which is of direct relevance to physiotherapy used during rehabilitation from stroke. Results from these studies should ultimately provide us with methods for improving recovery from stroke and potential therapies for learning and memory disorders.