Journal Article

Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity

Hinz, Rukun, Van der Linden, Annemie, Verhoye, Marleen, Peeters, Lore M., Missault, Stephan, De Vos, Winnok H., Keliris, Georgios A., Detrez, Jan R.

2020

Overview

The anterior cingulate area (ACC) is an integral part of the prefrontal cortex in mice and supports cognitive functions, including attentional processes, motion planning and execution as well as remote memory, fear and pain. Previous anatomical and functional imaging studies demonstrated that the ACC is interconnected with numerous brain regions, such as motor and sensory cortices, amygdala and limbic areas, suggesting it serves as a hub in functional networks. However, the exact role of the ACC in regulating functional network activity and connectivity remains to be elucidated. Recently developed neuromodulatory techniques, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) allow for precise control of neuronal activity. In this study, we used an inhibitory kappa-opioid receptor DREADD (KORD) to temporally inhibit neuronal firing in the right ACC of mice and assessed functional network activity and connectivity using non-invasive functional magnetic resonance imaging (MRI). We demonstrated that KORD-induced inhibition of the right ACC induced blood oxygenation-level dependent (BOLD) signal decreases and increases in connected brain regions of both hemispheres. More specifically, altered neuronal activity could be observed in functional brain networks including connections with sensory cortex, thalamus, basolateral amygdala and ventral pallidum, areas involved in attention processes, working memory, fear behavior and reward respectively. Furthermore, these modulations in neuronal activity were associated with decreased intra- and interhemispheric functional connectivity. Our results consolidate the hub role of the mouse ACC in functional networks and further demonstrate that the combination of the DREADD technology and non-invasive functional imaging methods is a valuable tool for unraveling mechanisms of network function and dysfunction by reversible inactivation of selected targets. •ACC differentially controls neuronal activity in specific functional brain networks.•ACC inhibition disrupts functional integrity in specific functional brain networks.•KOR-DREADDs - fMRI is a valuable tool for studying brain network functioning.

• Publisher: Elsevier Inc,Elsevier Limited,Elsevier
• Subject: Amygdala / Animals / Blood / Brain / Brain Mapping / Cerebral hemispheres / Cognitive ability / Default Mode Network - diagnostic imaging / Default Mode Network - drug effects / Designer receptors exclusively activated by designer drugs (DREADDs) / Drug dosages / Fear / Functional connectivity / Functional magnetic resonance imaging / Gyrus Cinguli - diagnostic imaging / Gyrus Cinguli - drug effects / Kappa-opioid receptor DREADDs (KORD) / Ligands / Magnetic Resonance Imaging / Memory / Mice / Narcotics / Neural Inhibition - drug effects / Neural networks / Neuroimaging / Neurological disorders / Neuronal activity / Neurons - drug effects / Opioid receptors (type kappa) / Pallidum (ventral) / Pharmacological functional MRI / Prefrontal cortex / Receptors, Opioid, kappa / Reinforcement / Resting state functional MRI / Short term memory / Somatosensory cortex / Thalamus