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Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation

41 Pages Posted: 20 Feb 2019 Publication Status: Published

See all articles by Valerio Zerbi

Valerio Zerbi

University of Zurich - Neuroscience Center Zurich; ETH Zürich - Neural Control of Movement Lab

Amalia Floriou-Servou

University of Zurich - Neuroscience Center Zurich

Marija Markicevic

University of Zurich - Neuroscience Center Zurich

Yannick Vermeiren

University of Antwerp - Laboratory of Neurochemistry and Behavior

Oliver Sturman

University of Zurich - Neuroscience Center Zurich

Mattia Privitera

University of Zurich - Neuroscience Center Zurich

Lukas von Ziegler

University of Zurich - Neuroscience Center Zurich

Kim David Ferrari

University of Zurich - Neuroscience Center Zurich

Bruno Weber

University of Zurich - Institute of Pharmacology and Toxicology

Peter Paul De Deyn

University of Antwerp - Laboratory of Neurochemistry and Behavior

Nici Wenderoth

University of Zurich - Neuroscience Center Zurich; ETH Zürich - Neural Control of Movement Lab

Johannes Bohacek

University of Zurich - Neuroscience Center Zurich

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Abstract

The locus coeruleus (LC) supplies norepinephrine (NE) to the entire forebrain, regulates many fundamental brain functions, and is implicated in several neuropsychiatric diseases. Although selective manipulation of the LC is not possible in humans, studies have suggested that strong LC activation might shift network connectivity to favor salience processing. To test this hypothesis, we use a mouse model to study the impact 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”. LC activation rapidly interrupts ongoing behavior and strongly increases brain-wide connectivity, with the most profound effects in the salience and amygdala networks. We reveal a direct correlation between functional connectivity changes and transcript levels of alpha-1, alpha-2, and beta-1 adrenoceptors across the brain, and a positive correlation between NE turnover and functional connectivity within select brain regions. These results represent the first brain-wide functional connectivity mapping in response to LC activation, and demonstrate a causal link between receptor expression, brain states and functionally connected large-scale networks at rest. 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.

Suggested Citation

Zerbi, Valerio and Floriou-Servou, Amalia and Markicevic, Marija and Vermeiren, Yannick and Sturman, Oliver and Privitera, Mattia and Ziegler, Lukas von and Ferrari, Kim David and Weber, Bruno and De Deyn, Peter Paul and Wenderoth, Nici and Bohacek, Johannes, Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation (February 15, 2019). Available at SSRN: https://ssrn.com/abstract=3334983 or http://dx.doi.org/10.2139/ssrn.3334983
This version of the paper has not been formally peer reviewed.

Valerio Zerbi

University of Zurich - Neuroscience Center Zurich ( email )

Rämistrasse 71
Zürich, CH-8006
Switzerland

ETH Zürich - Neural Control of Movement Lab ( email )

Switzerland

Amalia Floriou-Servou

University of Zurich - Neuroscience Center Zurich

Rämistrasse 71
Zürich, CH-8006
Switzerland

Marija Markicevic

University of Zurich - Neuroscience Center Zurich

Rämistrasse 71
Zürich, CH-8006
Switzerland

Yannick Vermeiren

University of Antwerp - Laboratory of Neurochemistry and Behavior

Prinsstraat 13
Antwerp, Antwerp 2000
Belgium

Oliver Sturman

University of Zurich - Neuroscience Center Zurich

Rämistrasse 71
Zürich, CH-8006
Switzerland

Mattia Privitera

University of Zurich - Neuroscience Center Zurich

Rämistrasse 71
Zürich, CH-8006
Switzerland

Lukas von Ziegler

University of Zurich - Neuroscience Center Zurich

Rämistrasse 71
Zürich, CH-8006
Switzerland

Kim David Ferrari

University of Zurich - Neuroscience Center Zurich

Rämistrasse 71
Zürich, CH-8006
Switzerland

Bruno Weber

University of Zurich - Institute of Pharmacology and Toxicology

Winterthurerstrasse 190
Zürich, CH-8057
Switzerland

Peter Paul De Deyn

University of Antwerp - Laboratory of Neurochemistry and Behavior

Prinsstraat 13
Antwerp, Antwerp 2000
Belgium

Nici Wenderoth

University of Zurich - Neuroscience Center Zurich ( email )

Rämistrasse 71
Zürich, CH-8006
Switzerland

ETH Zürich - Neural Control of Movement Lab ( email )

Switzerland

Johannes Bohacek (Contact Author)

University of Zurich - Neuroscience Center Zurich ( email )

Rämistrasse 71
Zürich, CH-8006
Switzerland

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