Concurrent high resolution calcium imaging and fMRI reveal intra anterior cingulate cortex neuronal activity and large-scale brain network connectivity in healthy and nicotine-addicted mice

并行高分辨率钙成像和功能磁共振成像揭示了健康和尼古丁成瘾小鼠的前扣带皮层神经元活动和大规模脑网络连接

• 批准号: 10576010
• 负责人: Li-MING Hsu
• 金额: $ 23.33万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576010
• 关键词: Address; Anatomy; Anesthesia procedures; Animals; Anterior; Attention; Attentional deficit; Behavioral; Brain; Calcium; Collaborations; Communication; Data; Dorsal; Emotions; Foundations; Functional Magnetic Resonance Imaging; Goals; Human; Image; Implant; Letters; Link; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mediating; Methodology; Microscope; Modeling; Morphologic artifacts; Motivation; Mus; Nature; Neurons; Nicotine; Nicotine Dependence; Predisposition; Prevention; Process; Property; Protocols documentation; Proxy; Reaction Time; Relapse; Resolution; Rest; Rewards; Rodent; Role; Signal Transduction; Stimulus; Stress; Techniques; Testing; Time; Work; addiction; awake; cingulate cortex; craving; executive function; imaging study; innovation; insight; mouse model; network dysfunction; neural; neurophysiology; novel; segregation; therapeutically effective

PROJECT SUMMARY Using functional magnetic resonance imaging (fMRI), studies have provided significant insights into unique large-scale functional organizations of the brain including default mode network (DMN) and salience network (SN). The aberrant communications of brain functional connectivity among these networks have been observed across different classes of addiction and are associated with craving and relapse. The overarching goal of this project is to identify the functional role of anterior cingulate cortex (ACC) in network integration in normal and addiction conditions. Our central hypotheses are that: 1) distinct functional clusters of neurons exist in rodent ACC and these clusters coactivate with distinct large-scale brain networks, 2) SN-related neurons in ACC will be activated in attention tasks whereas DMN-related neurons in ACC will be deactivated. 3) functional integration of SN-related neurons in ACC is decreased in nicotine addiction and causally relates to attention deficits via large-scale brain network dysfunctions. While fMRI can be utilized to depict large-scale brain networks, one technical challenge towards the testing of these hypotheses is to obtain spatially resolved neuronal activity within the ACC during fMRI. To address this, we will utilize an innovative MRI-compatible fluorescent miniature microscope, allowing concurrent imaging of ground-truth neuronal activities at cellular resolution during fMRI. We also implemented a silent zero-echo-time (ZTE) fMRI technique, enabling awake rodent imaging in a stress-free condition. Addressing these hypotheses will clarify the utility of ACC in predicting addiction related attention deficits and its putative role in serving as a novel treatment target for addiction. 1

项目摘要 使用功能磁共振成像（fMRI），研究为 大脑的独特大规模功能组织，包括默认模式网络（DMN）和显着性 网络（SN）。这些网络之间大脑功能连接的异常通信已经 在不同类别的成瘾中观察到，与渴望和复发有关。总体 该项目的目标是确定前扣带回皮层（ACC）在网络集成中的功能作用 正常和成瘾条件。我们的中心假设是：1）存在不同神经元的功能簇 在啮齿动物ACC和这些簇中与不同的大型脑网络共激活，2）与SN相关的神经元 ACC将在注意任务中激活，而ACC中与DMN相关的神经元将被停用。 3）功能 尼古丁成瘾中与SN相关神经元的整合在ACC中的整合降低，并因果关注 通过大型大脑网络功能障碍的缺陷。 fMRI可以用来描绘大型大脑 网络是测试这些假设的一个技术挑战是获得空间解决 fMRI期间ACC内的神经元活性。为了解决这个问题，我们将使用创新的MRI兼容 荧光微型显微镜，允许在细胞上同时对地面神经元活性进行成像 fMRI期间的分辨率。我们还实施了一种无声的零回波时间（ZTE）fMRI技术，使能够清醒 啮齿动物成像在无压力条件下。解决这些假设将阐明ACC预测的实用性 与成瘾相关的注意力缺陷及其在成为成瘾的新型治疗范围中的推定作用。 1