An analysis of synaptic plasticity at single synapses using the photolytically active AMPA receptor antagonist ANQX.

使用光解活性 AMPA 受体拮抗剂 ANQX 分析单个突触的突触可塑性。

• 批准号: G0701480/1
• 负责人: N Emptage
• 金额: $ 47.89万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701480%2F1
• 关键词: analysis; synaptic; plasticity; single; synapses

Perhaps the greatest challenge in contemporary biology is to understand the workings of the brain. The implications for such an understanding are almost boundless: From therapies with which to treat brain disorders through to recognizing the basis of self-awareness or consciousness, things that are the very essence of being human. The difficulties in achieving such goals are, predictably, as great as the rewards for success. In recent years significant advances in the field of light microscopy have revolutionised our ability to measure fundamental signalling processes within the cells the brain, the neurones. These measurements are achieved by introducing fluorescent dyes into individual brain cells and stimulating these dyes using precisely guided laser light. The dyes we use are specifically designed to change intensity in response to metabolic changes within the neurone, thus we are able to gather detailed information about activity within these cells simply by measuring changes in intensity of fluorescent light. In our current work we are using a fluorescent dye that changes intensity in response to a change in the calcium ion concentration within the neurone. An increase in calcium ions accompanies activity within neurones and so we are able to obtain a measure the level of activity by measuring increases in fluorescence. We also have a further method by which we can use light to measure biological processes. In this method we transform an inert compound into an active one. This is achieved by cutting a chemical bond with high intensity laser light. Using this approach we will investigate how neurones encode changes to their inputs, the synapses. The biological significance of changes at synapses is more profound than at first it may appear as these changes are thought to occur as an animal learns and stores new information to memory. Thus by examining these processes we hope to gain insight into the basic cellular mechanisms that underlie learning and memory.

也许当代生物学最大的挑战是理解大脑的运作。这种理解的意义几乎是无限的：从治疗大脑疾病的疗法到认识自我意识或意识的基础，这些都是人类的本质。可以预见，实现这些目标的困难与成功的回报一样大。近年来，光学显微镜领域的重大进展彻底改变了我们测量大脑细胞、神经元内基本信号过程的能力。这些测量是通过将荧光染料引入单个脑细胞并使用精确引导的激光刺激这些染料来实现的。我们使用的染料是专门设计来改变强度，以响应神经元内的代谢变化，因此我们能够通过测量荧光强度的变化来收集有关这些细胞内活动的详细信息。在我们目前的工作中，我们正在使用一种荧光染料，它的强度会随着神经元内钙离子浓度的变化而变化。钙离子的增加伴随着神经元内的活动，因此我们能够通过测量荧光的增加来测量活动水平。我们还有一种更进一步的方法，通过这种方法，我们可以用光来测量生物过程。在这种方法中，我们把一种惰性化合物转变成一种活性化合物。这是通过用高强度激光切割化学键来实现的。使用这种方法，我们将研究神经元如何编码它们的输入，突触的变化。突触变化的生物学意义比最初可能出现的更深刻，因为这些变化被认为是在动物学习和存储新信息时发生的。因此，通过研究这些过程，我们希望能够深入了解学习和记忆的基本细胞机制。