Functional imaging evidence for task-induced deactivation and disconnection of a major default mode network hub in the mouse brain
J. Ferrier, E. Tiran, T. Deffieux, M. Tanter, Z. Lenkei
Proceedings of the National Academy of Sciences June 15, 2020 DOI: 10.1073/pnas.1920475117 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Lightly sedated awake mice |
| Intervention | whisker stimulation |
| Topics | Default mode network |
| Key findings | Whisker stimulation in lightly sedated awake mice reduces activation and interhemispheric correlation in the retrosplenial cortex, a major hub of the default mode network, supporting an evolutionarily preserved DMN function. |
Abstract
Significance Our report first validates an imaging technique, functional ultrasound, an experimental approach providing significantly higher sensitivity and spatiotemporal resolution than fMRI, for the study of sensory stimulation-induced changes in activation and connectivity patterns in the awake mouse brain. Next, by using this approach in lightly sedated conscious mice, we provide functional evidence supporting an evolutionary preserved function of the default mode network, a set of highly connected brain areas, which is characteristically impaired in major neuropsychiatric diseases in humans. Uncovering the existence and function of the default mode network in mice, the main preclinical model organism for neuropsychiatric diseases, opens new avenues of high translational relevance for brain research and drug development. 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.
Comparable studies
Other preclinical and animal studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rat brains also have a default mode network Rats | 2012 | Observational study | |
| Large-scale topology and the default mode network in the mouse connectome Mouse brain | 2014 | Observational study | |
| Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network Anesthetized monkeys | 2016 | Observational study | |
| Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats Healthy rats and a rat model of alcohol relapse | 2023 | Randomized, placebo-controlled crossover pharmaco-fMRI study | |
| Altered functional connectivity within the default mode network in two animal models with opposing episodic memories Rats (control, LPS-challenged, and footshock-exposed groups) | 2018 | Animal model study |
Citations in the library
Cited by 6
- Ketamine-induced static and dynamic functional connectivity changes are modulated by opioid receptors and biological sex in rats. Neuropsychopharmacology April 19, 2025
- Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network. Nature Communications February 16, 2023
- Neuronal dynamics of the default mode network and anterior insular cortex: Intrinsic properties and modulation by salient stimuli. Science Advances February 15, 2023
- Subcortical control of the default mode network: Role of the basal forebrain and implications for neuropsychiatric disorders Brain Research Bulletin May 1, 2022
- Chemogenetic stimulation of tonic locus coeruleus activity strengthens the default mode network Science Advances April 1, 2022
and 1 more in the library
Cites 5
- A default mode of brain function Proceedings of the National Academy of Sciences January 16, 2001
- The Brain's Default Mode Network Annual Review of Neuroscience May 4, 2015
- Rat brains also have a default mode network Proceedings of the National Academy of Sciences February 21, 2012
- Large-scale topology and the default mode network in the mouse connectome Proceedings of the National Academy of Sciences December 15, 2014
- Functional connectivity in the resting brain: A network analysis of the default mode hypothesis Proceedings of the National Academy of Sciences December 27, 2002