Voltage dynamics of distinct cortical ensembles in visually guided behavior

视觉引导行为中不同皮质群的电压动态

基本信息

批准号：
10524557
负责人：
Madhuvanthi Kannan
金额：
$ 32.59万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10524557
关键词：
Address Affect Animals Attention BRAIN initiative Behavior Behavioral Brain Cells Classification Complement Computer software Cues Fluorescence Fluorescence Resonance Energy Transfer Funding Generations Genetic Goals Image Individual Interneurons Lighting Maps Measures Methods Modality Modeling Morphology Mus Neural Pathways Neurons Neurophysiology - biologic function Neurosciences Opsin Optics Pattern Perception Physiological Population Population Heterogeneity Primates Property Pyramidal Cells Reporting Research Resolution Rodent Role Running Sensory Speed Stimulus Structure Techniques Testing Time Variant Visual Visual Cortex Visual attention Work area striata attentional modulation awake behavioral outcome cellular targeting electrical property experimental study hippocampal pyramidal neuron imaging modality indexing insight instrumentation meter millisecond optogenetics postsynaptic response selective attention spatiotemporal tool transcriptomics visual processing voltage

项目摘要

ABSTRACT BRAIN Initiative-funded, large-scale approaches to classify neurons based on transcriptomic, morphological and electrical properties have unveiled dozens of unique cell classes in the mouse brain. However, whether they represent functionally diverse populations of relevance to animal perception and behavior remains an open question. Dissecting their individual roles requires the integration of targeted recording techniques and optogenetic manipulation approaches, which operate at the physiologically relevant spatiotemporal scales (i.e. cellular resolution and millisecond timescales). Here, we propose to use high-speed (0.4-1 kHz), genetically encoded fluorescence voltage imaging to understand the role of distinct interneuronal populations in attentional modulation of visual processing during visually guided behavior. First, we will establish the optical instrumentation for high-speed, dual channel voltage imaging with non-overlapping structured illumination. We will further validate the use of our second-generation, fluorescence resonance energy transfer (FRET)-opsin indicators Ace-mNeon2 and VARNAM2 and their reverse response polarity variants pAce and pAceR, for concurrent voltage recordings from pairs of interneuronal ensembles and pyramidal neurons in awake, running mice. Thereafter, using simultaneous triple-population voltage imaging, we will assess the effects of attention on the firing rates of the three cell classes during visually guided behavior and compute the spatiotemporal correlations in the activation patterns of neighboring neurons. Separately, we will measure the visual tuning properties of the same neurons during presentations of drifting grating stimuli. We will further draw a correlation between neuronal attention modulation index and feature selectivity to test the applicability of the feature similarity gain model. Lastly, to establish causal roles in the attentional modulation of visual responses, we will optogenetically manipulate the activity of select interneurons in a spatially precise manner, while recording the voltage responses in neighboring pyramidal cells when mice are engaged in the behavioral task. Our proposed work will (1) elucidate the role of distinct interneuron-types in visual attention and enable functional cross-comparisons within the same animals and at increased spatiotemporal resolution; (2) uncover synergistic and antagonistic relationships between neighboring pyramidal neuron-interneuron pairs for neurons that are positively versus negatively modulated by attention; (3) test the applicability of the feature similarity gain model in rodents and (4) establish causal roles for distinct interneuronal populations in attentional modulation of visual processing. Together, our work will establish simultaneous, multipopulation voltage imaging as the preferred modality to unravel the real-time functional differences between neuron-types in perception and behavior.

抽象的大脑倡议资助的大规模方法，用于基于转录组，形态学和电气特性已经在小鼠大脑中揭示了数十个独特的细胞类别。但是，他们是否代表功能多样的人群与动物感知和行为仍然是开放的问题。解剖其各个角色需要集成目标记录技术和光遗传操作方法，该方法在生理相关的时空尺度上运行（即细胞分辨率和毫秒的时间尺度）。在这里，我们建议使用高速（0.4-1 kHz），遗传编码的荧光电压成像了解不同的神经元中种群在视觉处理的注意调制中的作用视觉引导行为。首先，我们将建立用于高速，双通道电压的光学仪器具有非重叠的结构照明成像。我们将进一步验证第二代的使用，荧光共振能量转移（FRET） - 粘蛋白指标ACE-MNEON2和VARNAM2及其反向响应极性变体速度和起搏器，用于对成对内神经元的同时电压记录合奏和锥体神经元在醒着，运行老鼠。此后，使用同时进行三个人口电压成像，我们将评估注意力在视觉上对三个单元格的发射速率的影响引导行为并计算相邻神经元激活模式中的时空相关性。另外，我们将测量在漂移介绍期间相同神经元的视觉调谐特性光刺激。我们将进一步提出神经元注意调节指数和特征之间的相关性选择性测试特征相似性增益模型的适用性。最后，在视觉反应的注意调制，我们将在光遗传学上操纵精选中间神经元的活性以空间精确的方式，同时记录相邻锥体细胞中的电压响应从事行为任务。我们提出的工作将（1）阐明不同的中间类型在视觉注意力中的作用，并启用在同一动物中的功能性跨季子群体，并在增加时空分辨率下；（2）发现神经元的相邻锥体神经元互和之间的协同和拮抗关系积极而受到关注的负面调节；（3）测试特征相似性增益的适用性啮齿动物中的模型和（4）在注意调制中建立不同的神经间种群的因果关系视觉处理。一起，我们的工作将同时建立多种多样成像作为首选方式阐明在感知和行为中神经元类型之间的实时功能差异。