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

• 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
• 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

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 BRAIN Initiative 资助的大规模方法，根据转录组学、形态学和 电特性揭示了小鼠大脑中数十种独特的细胞类别。然而，无论他们 代表与动物感知和行为相关的功能多样化群体仍然是一个开放的问题 问题。剖析他们的个人角色需要整合有针对性的录音技术和 光遗传学操纵方法，在生理相关的时空尺度上运行（即 细胞分辨率和毫秒时间尺度）。 在这里，我们建议使用高速（0.4-1 kHz）、基因编码的荧光电压成像来 了解不同中间神经元群在视觉处理注意力调节中的作用 视觉引导的行为。首先，我们将建立高速、双通道电压的光学仪器 使用非重叠结构照明进行成像。我们将进一步验证我们第二代的使用， 荧光共振能量转移 (FRET)-视蛋白指示剂 Ace-mNeon2 和 VARNAM2 及其反向 响应极性变体 pAce 和 pAceR，用于来自中间神经元对的并发电压记录 清醒、奔跑的小鼠体内的神经元群和锥体神经元。此后，使用同时三重群体 电压成像，我们将评估视觉过程中注意力对三类细胞放电率的影响 引导行为并计算邻近神经元激活模式的时空相关性。 另外，我们将在漂移演示期间测量相同神经元的视觉调谐特性 光栅刺激。我们将进一步绘制神经元注意力调制指数和特征之间的相关性 选择性来测试特征相似度增益模型的适用性。最后，建立因果关系 视觉反应的注意力调节，我们将通过光遗传学操纵选定的中间神经元的活动 以空间精确的方式，同时记录小鼠时邻近锥体细胞的电压反应 从事行为任务。 我们提出的工作将（1）阐明不同的中间神经元类型在视觉注意力中的作用，并使得 在相同动物内以更高的时空分辨率进行功能交叉比较； (2)揭开 神经元相邻锥体神经元-中间神经元对之间的协同和拮抗关系 受到注意力的积极和消极调节； (3)测试特征相似度增益的适用性 啮齿动物模型，（4）建立不同中间神经元群体在注意力调节中的因果作用 视觉处理。 我们的工作将共同建立同步、多人电压成像作为首选模式 揭示神经元类型在感知和行为方面的实时功能差异。