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

项目摘要 使用功能性磁共振成像（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）和显著性 网络（SN）。这些网络之间的大脑功能连接的异常通信已经被发现。 在不同的成瘾类别中观察到，并与渴望和复发有关。总体 本项目的目的是确定前扣带皮层（ACC）在网络整合中的功能作用， 正常和成瘾状态。我们的中心假设是：1）存在不同的神经元功能簇 在啮齿动物ACC和这些簇与不同的大规模脑网络共激活，2）SN相关神经元， ACC在注意任务中被激活，而ACC中的DMN相关神经元将被去激活。3)功能 在尼古丁成瘾中，ACC中SN相关神经元的整合减少，并与注意力相关 通过大规模的大脑网络功能障碍来减少赤字。虽然功能磁共振成像可以用来描绘大规模的大脑 网络，对这些假设的测试的一个技术挑战是获得空间分辨 功能磁共振成像中前扣带回内的神经元活动。为了解决这个问题，我们将利用创新的MRI兼容 荧光微型显微镜，允许同时成像地面真实神经元活动在细胞 fMRI中的分辨率。我们还实施了一种无声的零回波时间（ZTE）功能磁共振成像技术， 无压力条件下的啮齿动物成像。解决这些假设将澄清行政协调会在预测的效用 成瘾相关的注意缺陷及其作为成瘾治疗新靶点的假定作用。 1

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