Optic Imaging of Fast Neural Activation Patterns in Brain Tissue

描述（由申请人提供）：对重要神经病（如癫痫和中风）的研究和治疗至关重要的是了解负责高级脑功能的神经元网络过程。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层内的并行处理，这可能是理想的，具有高的时间和空间分辨率的微创技术进行研究。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，这种方法的目标是近实时的，单轴突分辨率想象的重要并行处理，发生在复杂的神经元网络。该方法成像神经激活的几乎瞬时表现，并且最终应该能够提供动作电位传播的运动图像。我们将证明，该方法是能够成像，在反射模式和单轴突分辨率，局部光学双折射的变化，伴随着复杂的神经元网络的电活动，通过成像的光学偏振elipicity的变化。我们将首先开发一个能够成像单个神经（即小龙虾和/或龙虾）中的刺激活动的系统，然后在大鼠模型的下海马脑切片中进行测量。测试将包括成像癫痫发作诱导和药物反应的影响。该项目的结果将为未来两个重要的进展奠定基础：通过将双折射成像集成到切片显微镜中来对脑切片中的神经激活模式进行3-D成像，并最终在体内对小动物暴露的皮层中的激活模式进行实时成像。该提案的目的是开发一种微创方法，以高的时间和空间分辨率对孤立神经和小动物脑切片中的神经活动进行成像。这样的工具将有助于研究和治疗重要的神经病变，如癫痫和中风，并有助于了解负责更高大脑功能的神经元网络过程。

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.