Transcending dynamic and kinetic limits for neuronal calcium sensing

 描述（由申请人提供）：许多将信号从一个神经元传递到另一个神经元的途径都涉及钙作为信使分子。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内相互作用。该实验室的一个长期目标是生产指标，可以跟踪在行为动物的大量神经元在几天到几周内的钙变化的全方位。特别是，拟议的实验将产生新技术，可以跟踪参与重要大脑功能的神经元细胞类型的活动，从精细运动控制到奖励学习。本申请的总体目标是设计探针，可以在清醒的，行为动物的rapi神经活动，并证明其在研究细胞类型的活性不能使用目前可用的技术记录的有用性。这一贡献意义重大，因为它将使研究人员能够在现实条件下研究重要神经回路的功能。这种方法是创新的，因为该实验室将开发工具，允许研究以前无法在清醒动物中检查的细胞。因此，本申请中提出的工作将提高我们理解大脑在健康和疾病中如何运作的能力。从长远来看，这些信息可能会导致诊断，治疗和预防各种脑部疾病的新方法。

 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.