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疾病的研究和治疗至关重要的是对负责高级大脑功能的神经网络过程的了解。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进行研究。这项建议的目的是开发一种微创的方法，在分离的神经和小动物脑片中成像神经活动。具体地说，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。该方法成像神经激活的近乎瞬时的表现，并最终应该能够提供动作电位传播的运动图像。我们将通过成像光学偏振椭圆度的变化来证明该方法能够在反射模式和单轴分辨率下成像复杂神经网络中伴随电活动的局部光学双折射变化。我们将首先开发一个能够对单个神经(即小龙虾和/或龙虾)的刺激活动进行成像的系统，然后在大鼠模型的校园脑片上进行测量。测试将包括对癫痫诱导和药物反应的影响进行成像。该项目的结果将为未来的两个重要进展奠定基础：通过将双折射成像整合到切片显微镜中来对大脑切片中的神经激活模式进行3D成像，并最终在活体内实时成像小动物暴露的皮质中的激活模式。这项建议的目的是开发一种具有高时间和空间分辨率的在分离的神经和小动物脑片中成像神经活动的微创方法。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，并有助于了解负责更高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.