Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation

Publication date: Available online 18 June 2019Source: NeuronAuthor(s): Valerio Zerbi, Amalia Floriou-Servou, Marija Markicevic, Yannick Vermeiren, Oliver Sturman, Mattia Privitera, Lukas von Ziegler, Kim David Ferrari, Bruno Weber, Peter Paul De Deyn, Nicole Wenderoth, Johannes BohacekSummaryThe 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.Graphical Abstract

Source: Neuron - June 20, 2019 Category: Neuroscience Source Type: research