Functional imaging evidence for task-induced deactivation and disconnection of a major default mode network hub in the mouse brain
Functional imaging evidence for task-induced deactivation and disconnection of a major default mode network hub in the mouse brain
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DOI：
10.1073/pnas.1920475117
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发表时间：
2020-06-30
影响因子：
11.1
通讯作者：
Lenkei, Zsolt
中科院分区：
文献类型：
--
作者：
Ferrier, Jeremy;Tiran, Elodie;Lenkei, Zsolt
默认模式网络（DMN）在功能性脑成像研究中被定义为一组高度连接的大脑区域，这些区域在清醒休息时活跃，在基于任务的刺激期间失活。DMN功能在主要的神经精神疾病中特征性受损，强调了其转化研究的兴趣。然而，在小鼠（一种主要的临床前啮齿动物模型）中，仍然没有功能成像证据支持DMN在高要求的认知/感觉任务期间失活和解连接。在这里，我们已经开发了功能性超声（fUS）成像，以正确地可视化激活水平和功能连接模式，在头部限制清醒和行为的小鼠，并调查他们的调制过程中的感觉任务，胡须刺激。我们确定了可重复的和高度对称的静息状态网络，整体连接强度与动物的觉醒水平成正比。我们发现，单侧胡须刺激导致轻度镇静小鼠对侧桶皮质的预期激活，而半球间抑制减少同侧桶皮质的活动。胡须刺激也会导致海马体中双边连接的升高。重要的是，除了这些触觉信息处理的主要枢纽的功能变化，在真正清醒的休息状态期间，胡须刺激导致高度特异性的减少，在restrosimenial皮质，DMN的主要枢纽内的激活和半球间的相关性。这些结果验证了用于研究轻度镇静清醒小鼠大脑中的激活和连接的成像技术，并提供了支持DMN进化保留功能的证据，从而提高了神经精神疾病临床前模型的翻译相关性。
The default mode network (DMN) has been defined in functional brain imaging studies as a set of highly connected brain areas, which are active during wakeful rest and inactivated during task-based stimulation. DMN function is characteristically impaired in major neuropsychiatric diseases, emphasizing its interest for translational research. However, in the mouse, a major preclinical rodent model, there is still no functional imaging evidence supporting DMN deactivation and deconnection during high-demanding cognitive/sensory tasks. Here we have developed functional ultrasound (fUS) imaging to properly visualize both activation levels and functional connectivity patterns, in head-restrained awake and behaving mice, and investigated their modulation during a sensory-task, whisker stimulation. We identified reproducible and highly symmetric resting-state networks, with overall connectivity strength directly proportional to the wakefulness level of the animal. We show that unilateral whisker stimulation leads to the expected activation of the contralateral barrel cortex in lightly sedated mice, while interhemispheric inhibition reduces activity in the ipsilateral barrel cortex. Whisker stimulation also leads to elevated bilateral connectivity in the hippocampus. Importantly, in addition to functional changes in these major hubs of tactile information processing, whisker stimulation during genuine awake resting-state periods leads to highly specific reductions both in activation and interhemispheric correlation within the restrosplenial cortex, a major hub of the DMN. These results validate an imaging technique for the study of activation and connectivity in the lightly sedated awake mouse brain and provide evidence supporting an evolutionary preserved function of the DMN, putatively improving translational relevance of preclinical models of neuropsychiatric diseases.