Label-free 4D optical detection of neural activity

无标记 4D 光学检测神经活动

• 批准号: 9056250
• 负责人: MAKSIM V BAZHENOV
• 金额: $ 23.13万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9056250
• 关键词: 4-Aminopyridine; Acute; Animal Model; Blood flow; Brain; Brain imaging; Categories; Cells; Characteristics; Contrast Media; Data; Detection; Electric Stimulation; Electrodes; Electrophysiology (science); Epilepsy; Event; Fluorescence; Focal Seizure; Functional Imaging; Future; Generalized seizures; Genetic; Geometry; Grant; Health; Hippocampus (Brain); Human; Image; Imaging Techniques; In Vitro; Knowledge; Label; Lead; Light; Measurement; Measures; Methods; Mission; Modification; Neurons; Neurosciences; Optical Coherence Tomography; Optics; Pathologic; Pathway interactions; Phase; Physiological; Population; Protocols documentation; Public Health; Quality of life; Refractive Indices; Research; Resolution; Sampling; Sensitivity and Specificity; Signal Transduction; Site; Slice; Source; Surface; Synapses; System; Techniques; Time; TimeLine; Tissues; Validation; base; brain tissue; extracellular; falls; imaging modality; improved; in vitro Model; in vitro activity; in vivo; innovation; innovative technologies; millimeter; millisecond; multi-electrode arrays; multidisciplinary; neural circuit; neuroimaging; novel; optical imaging; optogenetics; public health relevance; relating to nervous system; research study; scale up; signal processing; spatiotemporal; temporal measurement; tool

 DESCRIPTION (provided by applicant): The ideal neuroimaging technique would provide exquisite structural detail and also provide functional information, with high spatial and temporal resolution. Optical coherence tomography (OCT) is an optical imaging technique in which light from a low coherent source illuminates tissue and reflectivity of internal microstructures at different depths is measured by an interferometer. OCT is capable of micrometer-spatial and millisecond-temporal resolutions, without the use of exogenous contrast agents (hence "label-free"). The objective in this application is to develop and validate OCT for mammalian brain functional imaging; correlate OCT images with cellular electrophysiology assessed by multielectrode array (MEA); and provide proof-of- principle for OCT-based detection of neural activity. Two specific aims will be pursued: (1) Validate detection of multi-unit activity (MUA) by optical coherence tomography (OCT) in hippocampal slices. Our previous data demonstrate that OCT can detect synchronous cellular firing associated with both generalized and focal seizure activity. However, the sensitivity of OCT to physiological events such as multiunit activity (MUA) has not yet been determined. In this Aim, MUA induced by 4-aminopyridine (4-AP) and high K+ will be correlated to OCT. (2) Validate detection of local stimulation-induced synaptic activation by OCT. To allow more precise control of local stimulation site and intensity, in this Aim we will use local stimulation of a defined synaptic pathway in the hippocampal slice combined with OCT-based detection. Stimulation of the Schaffer collateral pathway from CA3 to CA1 will be performed by (1) electrical stimulation and (2) optogenetic stimulation to trigger MUA in CA1 that will be then detected by MEA and correlated to the changes in the optical signal by OCT. Our approach is innovative in adapting OCT for brain functional imaging. The proposed research is significant because it will lead to the validation of OCT as a neuroimaging tool for research in neuroscience.

 描述（应用程序提供）：理想的神经影像学技术将提供独家的结构细节，并提供功能信息，并具有高空间和临时的 解决。光学相干断层扫描（OCT）是一种光学成像技术，其中低相干源的光照亮组织和不同深度下内部微观结构的反射率，通过干涉仪测量。 OCT能够无需使用外源性对比剂（因此“无标签”），能够进行微米空间和毫秒的分辨率。该应用程序的目的是开发和验证哺乳动物脑功能成像的OCT；通过多电极阵列（MEA）评估的细胞电生理学将OCT图像与细胞电生理相关；并提供基于OCT的神经活动检测的原理。将追求两个具体目标：（1）验证检测多单元活动（MUA） 海马切片中的光学相干断层扫描（OCT）。我们以前的数据表明，OCT可以检测与广义和局灶性癫痫活性相关的同步细胞发射。然而，尚未确定OCT对多个活性（MUA）等物理事件的敏感性。在此目标中，由4-氨基吡啶（4-AP）诱导的MUA和高K+将与OCT相关。 （2）通过OCT验证检测局部刺激诱导的合成激活。为了更精确地控制局部刺激位点和强度，在此目的中，我们将使用对海马切片中定义的突触途径的局部刺激，并结合了OCT基于OCT的检测。 （1）电刺激和（2）光遗传学刺激触发Ca1中的MUA，然后通过MEA检测到MEA，并与OCT到OCT的光学信号的变化相关，从而通过（1）电刺激刺激了从CA3到CA1进行的Schaffer侧支途径的刺激。我们的方法是为了使OCT适应大脑功能成像的创新性。拟议的研究很重要，因为它将导致OCT作为神经科学研究的神经影像学工具的验证。