Use of Calcium Indicator Proteins in Spike Counting Mode

 描述(申请人提供)：大脑计划的一个长期目标是跟踪表现良好的动物体内大量神经元的活动，从而捕捉到大脑电路完成的信息处理。神经元活跃时的一个普遍信号是信使离子钙。通过检测单个神经元中每个动作电位后钙离子浓度的变化，研究人员可以追踪该神经元的活动，但目前这种方法的时间分辨率有限。总的目标是 这一应用是在脉冲计数模式下使用钙敏感探针来检测个体动作电位作为空间和时间上的离散事件。拟议中的实验将产生一种新技术，可以一次在数百到数千个神经元中以毫秒级的分辨率跟踪活动。这一贡献意义重大，因为它将允许研究人员以毫秒级的分辨率非侵入性地成像清醒动物的重要神经回路。这种方法是创新的，因为研究人员将使用一种非常受欢迎的钙传感器蛋白的新颖、超快反应模式来获得否则不可能实现的时间分辨率。因此，这项申请中提出的工作提高了我们理解大脑如何在健康和疾病中发挥作用的能力。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): A long-term goal of the BRAIN Initiative is to track activity in large numbers of neurons individually in behaving animals, thus capturing the information processing that is done by brain circuitry. A universal signal in neurons when they are active is the messenger ion calcium. By examining changes in calcium concentration following each action potential in an individual neuron, researchers can track that neuron's activity, but at present, the time resolution of this approach is limited. The overall objective of this application is to use calcium-sensitive probes in spike-counting mode to detect individual action potentials as discrete events in space and time. The proposed experiments will produce new technology that can follow activity with millisecond resolution in hundreds to thousands of neurons at once. This contribution is significant because it will allow researchers to image important neural circuits noninvasively with millisecond resolution in awake animals. This approach is innovative because the investigators will use a novel, ultrafast response mode of a highly popular calcium sensor protein to obtain time resolution that is not otherwise possible. The work proposed in this application therefore advances 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.