Format

Send to

Choose Destination
Neuron. 2019 Jun 7. pii: S0896-6273(19)30487-8. doi: 10.1016/j.neuron.2019.05.034. [Epub ahead of print]

Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation.

Author information

1
Neural Control of Movement Lab, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland; Neuroscience Center Zürich, ETH Zürich and University of Zürich, Zürich, Switzerland. Electronic address: valerio.zerbi@hest.ethz.ch.
2
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland; Neuroscience Center Zürich, ETH Zürich and University of Zürich, Zürich, Switzerland.
3
Neural Control of Movement Lab, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland; Neuroscience Center Zürich, ETH Zürich and University of Zürich, Zürich, Switzerland.
4
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Wilrijk (Antwerp), Belgium; Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, the Netherlands.
5
Experimental Imaging and Neuroenergetics, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland; Neuroscience Center Zürich, ETH Zürich and University of Zürich, Zürich, Switzerland.
6
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Wilrijk (Antwerp), Belgium; Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, the Netherlands; Department of Neurology, Memory Clinic of Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
7
Neural Control of Movement Lab, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland; Neuroscience Center Zürich, ETH Zürich and University of Zürich, Zürich, Switzerland. Electronic address: nicole.wenderoth@hest.ethz.ch.
8
Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland; Neuroscience Center Zürich, ETH Zürich and University of Zürich, Zürich, Switzerland. Electronic address: johannes.bohacek@hest.ethz.ch.

Abstract

The locus coeruleus (LC) supplies norepinephrine (NE) to the entire forebrain and regulates many fundamental brain functions. Studies in humans have suggested that strong LC activation might shift network connectivity to favor salience processing. To causally test this hypothesis, we use a mouse model to study the effect of LC stimulation on large-scale functional connectivity by combining chemogenetic activation of the LC with resting-state fMRI, an approach we term "chemo-connectomics." We show that LC activation rapidly interrupts ongoing behavior and strongly increases brain-wide connectivity, with the most profound effects in the salience and amygdala networks. Functional connectivity changes strongly correlate with transcript levels of alpha-1 and beta-1 adrenergic receptors across the brain, and functional network connectivity correlates with NE turnover within select brain regions. We propose that these changes in large-scale network connectivity are critical for optimizing neural processing in the context of increased vigilance and threat detection.

KEYWORDS:

DREADDs; anxiety; chemogenetics; functional connectivity; locus coeruleus; noradrenaline; resting-state functional magnetic resonance imaging; rs-fMRI; salience; stress

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center