Optic Imaging of Fast Neural Activation Patterns in Brain Tissue

描述（由申请人提供）：对癫痫和中风等重要神经病的研究和治疗至关重要的是了解负责高级脑功能的神经网络过程。复杂的、高度相互关联的功能，如记忆、决策和运动控制，依赖于皮质内并行处理，理想情况下，可以用具有高时间和空间分辨率的微创技术来研究。本提案的目的是开发一种微创方法，在孤立的神经和小动物脑切片中成像神经活动。具体来说，这种方法的目标是对复杂神经元网络中发生的重要并行处理进行近实时、单轴突分辨率的想象。该方法能对神经活动的近瞬时表现进行成像，并最终能够提供动作电位传播的动态图像。我们将证明，该方法能够成像，在反射模式和单轴突分辨率下，局部光学双折射变化，伴随电活动在复杂的神经网络中，通过成像的光学偏振性的变化。我们将首先开发一个能够成像单个神经（如小龙虾和/或龙虾）受刺激活动的系统，然后在大鼠模型的下丘脑脑切片中进行测量。测试将包括成像诱发癫痫发作和药物反应的影响。该项目的结果将为两个重要的未来进展奠定基础：通过将双折射成像集成到切片显微镜中，在大脑切片中进行神经激活模式的三维成像；最终，在活体小动物暴露的皮层中进行激活模式的实时成像。本提案的目的是开发一种微创方法，在孤立的神经和小动物脑切片中成像神经活动，具有高时间和空间分辨率。这种工具将有助于研究和治疗重要的神经疾病，如癫痫和中风，并有助于了解负责高级大脑功能的神经网络过程。

DESCRIPTION (provided by applicant): Vital to the study and treatment of important neuropathies, such as epilepsy and stroke is an understanding of the neuronal network processes responsible for higher brain functions. Complex, highly interconnected functions such as memory, decision making, and motor control depend on intracortical parallel processing, which may be investigated, ideally, with a minimally invasive technology having both high temporal and spatial resolution. The objective of this proposal is to develop a minimally-invasive method of imaging neural activity in isolated nerves and in small animal brain slices. Specifically, this method targets near-real-time, single-axon resolution imagining of the important parallel processing that occurs in complex neuronal networks. The method images nearly-instantaneous manifestations of neural activation, and should ultimately be able to provide moving-picture images of action potential propagation. We will demonstrate that the method is capable of imaging, in reflectance mode and with single- axon resolution, the local optical birefringence changes that accompany electrical activity in complex neuronal networks by imaging the changes in optical polarization elipticity. We will first develop a system capable of imaging the stimulated activity in individual nerves (i.e. crayfish and/or lobster) and then progress to measurements in hypocampus brain slices from a rat model. Testing will include imaging the effects of seizure induction and drug response. Results of this project will lay the groundwork for two important future advances: 3-D imaging of neural activation patterns in brain slices by integration of the birefringence imaging into sectioning microscopy and, ultimately, real-time imaging of activation patterns in the exposed cortex of small animals, in vivo. The objective of this proposal is to develop a minimally-invasive method of imaging neural activity in isolated nerves and in small animal brain slices, with high temporal and spatial resolution. Such a tool will aid in the study and treatment of important neuropathies, such as epilepsy and stroke, and can help provide an understanding of the neuronal network processes responsible for higher brain functions.