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

项目概要 利用功能磁共振成像 (fMRI)，研究提供了重要的见解： 大脑独特的大规模功能组织，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被 在不同类别的成瘾中观察到，并且与渴望和复发有关。首要的 该项目的目标是确定前扣带皮层（ACC）在网络整合中的功能作用 正常和成瘾条件。我们的中心假设是：1）存在不同功能的神经元簇 在啮齿动物 ACC 中，这些簇与不同的大规模大脑网络共同激活，2) SN 相关神经元 ACC 将在注意力任务中被激活，而 ACC 中与 DMN 相关的神经元将被停用。 3）功能性 尼古丁成瘾时 ACC 中 SN 相关神经元的整合减少，并且与注意力有因果关系 大规模脑网络功能障碍导致的缺陷。虽然功能磁共振成像可以用来描绘大范围的大脑 网络中，测试这些假设的一项技术挑战是获得空间分辨率 fMRI 期间 ACC 内的神经元活动。为了解决这个问题，我们将利用一种创新的 MRI 兼容 荧光微型显微镜，允许同时对细胞内的真实神经元活动进行成像 fMRI 期间的分辨率。我们还实施了无声零回波时间 (ZTE) fMRI 技术，能够实现清醒状态 在无压力的条件下进行啮齿动物成像。解决这些假设将阐明 ACC 在预测方面的效用 成瘾相关的注意力缺陷及其在成瘾新治疗目标中的假定作用。 1