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

项目总结 使用功能磁共振成像(FMRI)，研究提供了重要的见解 独特的大规模大脑功能组织，包括默认模式网络(DMN)和突显 网络(SN)。这些网络之间大脑功能连接的异常通信一直是 在不同的成瘾类别中都可以观察到，并与渴望和复发有关。最重要的是 本项目的目标是确定前扣带回(ACC)在网络整合中的功能作用。 正常和上瘾状态。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脑网络共同激活，2)在 在注意任务中，ACC将被激活，而ACC中与DMN相关的神经元将被去激活。3)功能 尼古丁成瘾大鼠下丘脑皮质黑质神经元整合减少与注意力相关 通过大规模大脑网络功能障碍造成的缺陷。而功能磁共振成像可以用来描绘大规模的大脑 网络，测试这些假说的一个技术挑战是获得空间解析 在功能磁共振成像过程中，ACC内的神经元活动。为了解决这一问题，我们将利用与MRI兼容的创新 荧光微型显微镜，可同时成像细胞内真实的神经元活动 功能磁共振成像过程中的分辨率。我们还实施了静默零回声时间(ZTE)功能磁共振技术，支持唤醒 无应激状态下的啮齿动物成像。解决这些假设将澄清ACC在预测中的效用 与成瘾相关的注意力缺陷及其作为新的成瘾治疗靶点的推定作用。 1