An investigation of action potential triggered calcium release from a lysosomal store in hippocampal neurones

动作电位的研究触发海马神经元溶酶体储存的钙释放

• 批准号: G0501572/1
• 负责人: N Emptage
• 金额: $ 49.94万
• 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: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501572%2F1
• 关键词: investigation; action; potential; triggered; calcium

One of most exciting challenges in contemporary science is to unravel the workings of the brain. It is a challenge on many levels that has brought together researchers from diverse fields of biology, physics and psychology. The implications for such research are profound: from the development of therapies against neurodegenerative and psychobiological diseases, to understanding the computational properties of the brain. Within the brain diverse functions such as neuronal cell development, learning and degeneration are all dependent on dynamic calcium ion signals. Malfunctions in calcium ion signalling may underlie disorders such as Alzheimers disease and epilepsy. Modern fluorescent microscopy techniques allow detection of changes in the intracellular concentration of calcium ions. Using these techniques in combination with pharmacology we have identified a novel mechanism by which neurones regulate calcium ion level during activity; a structure known as the lysosome, more typically associated with cellular metabolism, appears to release calcium ions in response to neuronal activity.Our current work is focused on resolving more finely the patterns of calcium ion release from the lysosome. Genetic tools will be used to identify the way neuronal activity is detected by the lysosome. Electron microscopy will reveal the precise cellular location of this calcium ion store. Examining precisely how the lysosome regulates intracellular calcium ions will add a new dimension to our understanding of the complex roles of this ion.

当代科学中最令人兴奋的挑战之一是解开大脑的运作机制。这是一个多层面的挑战，来自生物学、物理学和心理学不同领域的研究人员聚集在一起。此类研究的影响是深远的：从针对神经退行性疾病和心理生物学疾病的疗法的开发，到了解大脑的计算特性。在大脑中，神经细胞发育、学习和退化等多种功能都依赖于动态钙离子信号。钙离子信号传导故障可能是阿尔茨海默病和癫痫等疾病的根源。现代荧光显微镜技术可以检测细胞内钙离子浓度的变化。将这些技术与药理学相结合，我们已经确定了神经元在活动期间调节钙离子水平的新机制；一种称为溶酶体的结构，通常与细胞代谢相关，似乎会响应神经元活动而释放钙离子。我们目前的工作重点是更精细地解析溶酶体释放钙离子的模式。遗传工具将用于识别溶酶体检测神经元活动的方式。电子显微镜将揭示钙离子存储的精确细胞位置。精确检查溶酶体如何调节细胞内钙离子将为我们理解该离子的复杂作用增加一个新的维度。