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

当代科学中最激动人心的挑战之一是揭开大脑的工作原理。这是一个多层面的挑战，汇集了来自生物、物理和心理学不同领域的研究人员。这类研究的意义是深远的：从开发针对神经退行性疾病和心理生物学疾病的治疗方法，到了解大脑的计算特性。在大脑中，神经细胞的发育、学习和退化等多种功能都依赖于动态的钙离子信号。钙离子信号的故障可能是阿尔茨海默氏病和癫痫等疾病的基础。现代荧光显微镜技术可以检测细胞内钙离子浓度的变化。结合使用这些技术和药理学，我们已经确定了一种新的机制，神经元通过它来调节活动中的钙离子水平；一种被称为溶酶体的结构，更典型地与细胞代谢有关，似乎响应神经元的活动而释放钙离子。我们目前的工作集中在更精细地解决溶酶体释放钙离子的模式。基因工具将被用来确定溶酶体检测神经元活动的方式。电子显微镜将揭示这个钙离子储存库的精确细胞位置。精确研究溶酶体如何调节细胞内钙离子将为我们理解这种离子的复杂作用增加一个新的维度。

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.