Dissecting neocortical field potential dynamics using optical voltage imaging in genetically targeted cell-types

使用光学电压成像在基因靶向细胞类型中剖析新皮质场电位动态

基本信息

批准号：
10338619
负责人：
MARK J SCHNITZER
金额：
$ 198.29万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-25 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10338619
关键词：
Animals Area Astrocytes BRAIN initiative Behavior Brain Brain Diseases Cells Clinical Cognition Collection Color Complement 2 Computer Models Computers Conscious Cre driver Data Set Deposition Diagnosis Dissection Distal Electrocorticogram Electrodes Electroencephalography Ensure Event-Related Potentials Excision Fiber Optics Foundations Gene Expression Goals Grant Head Human Image Individual Interneurons Joints Location Maps Measurement Membrane Methods Microscopy Morphology Mus Neocortex Neurons Neurosciences Operative Surgical Procedures Optics Phase Physiological Population Prefrontal Cortex Property Pyramidal Cells Resolution Role Shapes Signal Transduction Site Speed Stimulus Study models Surface Synapses Techniques Testing Time Tissues Transgenic Mice Transgenic Organisms Travel United States National Institutes of Health Variant Visual Cortex Work awake biophysical model brain research brain tissue cell type designer receptors exclusively activated by designer drugs electric field electrical measurement experimental study extracellular hippocampal pyramidal neuron insight instrumentation neocortical novel open data optical fiber public repository relating to nervous system spatiotemporal tool voltage

项目摘要

Measurements of cortical field potentials are widely used throughout basic and clinical neuroscience, including in electroencephalography (EEG), electrocorticography (ECoG) and local field potential (LFP) recordings. However, the neural origins of field potentials remain poorly understood, due to a lack of techniques for dissecting how different classes of cells contribute to field potential signals. To overcome this longstanding barrier, our project applies fluorescent voltage-indicators and instrumentation for optical voltage-imaging that our team created earlier in the NIH BRAIN Initiative. These new tools will enable us to systematically identify the contributions of 12 different cell-types to neocortical field potential activity. To perform cell-type specific recordings of neural transmembrane voltage dynamics, we will express red and green genetically encoded voltage indicators in a wide set of different transgenic mouse lines, each of which allows selective gene expression in one of the pyramidal neuron or interneuron classes of the neocortex. Concurrent with optical recordings, we will perform traditional electrical recordings of cortical LFPs. These joint optical and electrical measurements will be the first of their kind and will yield important insights into how each neuron-type influences spontaneous and stimulus-evoked cortical field potential activity. Across our collection of mouse lines, we will conduct 3 novel types of recordings, each of which uses cutting-edge instrumentation for optical voltage-imaging in up to 2 cell-types at once in awake behaving mice: a) Fiber-optic voltage-sensing, for tracking the voltage dynamics of genetically defined neural populations; b) Wide-field voltage-imaging of voltage oscillations and waves across the cortex in specific cell-types; c) High-speed (1 kHz) optical voltage imaging of spiking dynamics in up to 2 neuron-types at a time. Further, to test the causal role of each neuron class in shaping cortical field potentials, we will also perform chemogenetic inhibition studies in each of the mouse lines. In these studies, we will silence each of the individual neuron-types and observe how the effective removal of this cell-type from cortical circuitry impacts both LFP activity and the population voltage dynamics of other neuron classes. Together, these groundbreaking studies will propel understanding of cortical field potentials in basic and applied neuroscience by providing fundamental insights into how different cell-types shape field potential dynamics. To help assure that our experiments optimally advance conceptual understanding in the field, our team includes 2 computational neuroscientists whose expertise lies in modeling the biophysics of cortical field potentials. To promote transparency and open-science, we will deposit all of the extensive datasets and analyses from our experiments into public repositories.

在基本和临床神经科学中广泛使用了皮质场电位的测量值，包括脑电图（EEG），电皮质学（ECOG）和局部田间电位（LFP）记录。然而，由于缺乏解剖不同类别的细胞对现场电位信号的贡献的技术缺乏技术，因此田间电位的神经起源仍然很少理解。为了克服这个长期存在的障碍，我们的项目应用了荧光电压指示剂和仪器，用于我们团队在NIH大脑计划中创建的光电压成像。这些新工具将使我们能够系统地确定12种不同细胞类型对新皮层田间潜在活性的贡献。为了执行神经跨膜电压动力学的细胞类型特异性记录，我们将在各种不同的转基因小鼠系中表达红色和绿色遗传编码的电压指示器，每种均可在锥体神经元或新皮层的跨性神经元中选择性基因表达。同时与光学记录同时进行皮质LFP的传统电记录。这些关节光学测量和电气测量将是它们的第一个，并将对每个神经元型如何影响自发和刺激引起的皮质场潜在活性产生重要的见解。在我们的鼠标系列集合中，我们将进行3种新型的录音类型，每种录音都使用尖端的仪器，用于在醒着的行为醒目的小鼠中一次最多2个细胞类型来进行光电压成像：a）纤维上的电压感应，以跟踪遗传定义的神经群体的电压动力学； b）特定细胞类型中皮质的电压振荡和波浪的宽场电压成像； c）一次高速动力学的高速（1 kHz）光电压成像一次，一次最多2个神经元类型。此外，为了测试每个神经元类在塑造皮质场电位中的因果作用，我们还将在每种小鼠系中进行化学遗传抑制研究。在这些研究中，我们将使每个单个神经元类型都保持沉默，并观察到该细胞类型从皮质电路中的有效去除如何影响LFP活性和其他神经元类别的种群电压动力学。这些开创性的研究一起，将通过提供有关不同细胞类型如何影响场电位动力学的基本见解，从而推动对基本和应用神经科学中皮质场电位的理解。为了确保我们的实验在该领域最佳地促进概念理解，我们的团队包括2个计算神经科学家，其专业知识在于对皮质场电位的生物物理学进行建模。为了促进透明度和开放科学，我们将将实验中的所有广泛数据集和分析存入公共存储库中。