Transcending dynamic and kinetic limits for neuronal calcium sensing

 描述(申请人提供)：许多将信号从一个神经元传递到另一个神经元的途径涉及到钙作为信使分子。通过检查单个神经元内钙浓度的变化，研究人员可以了解这些神经元如何在电路中相互作用。这个实验室的一个长期目标是生产能够跟踪动物行为的大量神经元在几天到几周内钙变化的指标。特别是，拟议中的实验将产生新的技术，可以跟踪与重要大脑功能有关的神经细胞类型的活动，从精细运动控制到奖励学习。这项应用的总体目标是设计能够跟踪清醒、行为动物的中缝神经活动的探针，并证明它们在研究使用当前可用的技术无法记录其活动的细胞类型方面的有效性。这一贡献意义重大，因为它将使研究人员能够研究现实条件下重要神经回路的功能。这种方法是创新的，因为这个实验室将开发工具，允许研究以前无法在清醒动物身上检测的细胞。因此，这项申请中提出的工作将提高我们了解大脑在健康和疾病中的功能的能力。从长远来看，这些信息可能导致诊断、治疗和预防各种大脑疾病的新方法。

 DESCRIPTION (provided by applicant): Many pathways that carry signals from one neuron to another involve calcium as a messenger molecule. By examining changes in calcium concentration within individual neurons, researchers can learn how these neurons interact within circuits. A long-term goal of this laboratory is to produce indicators that can track the full rang of calcium changes in large numbers of neurons in behaving animals across days to weeks. In particular, the proposed experiments will produce new technology that can follow activity in neuronal cell types that are involved in important brain functions, from fine motor control to reward learning. The overall objective of this application is to design probes that can follow rapi neural activity in awake, behaving animals and to demonstrate their usefulness in studying cell types whose activity cannot be recorded using currently available techniques. This contribution is significant because it will allow researchers to investigate the function of important neural circuits under realistic conditions. This approach is innovative because this laboratory will develop tools that allow the study of cells that previously could not be examined in awake animals. The work proposed in this application will therefore advance our ability to understand how the brain functions in health and disease. In the long run, this information could lead to new approaches to diagnosis, treatment, and prevention of a variety of brain disorders.