Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity
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 AC...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811920305747 |
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| author | Lore M. Peeters Rukun Hinz Jan R. Detrez Stephan Missault Winnok H. De Vos Marleen Verhoye Annemie Van der Linden Georgios A. Keliris |
| author_facet | Lore M. Peeters Rukun Hinz Jan R. Detrez Stephan Missault Winnok H. De Vos Marleen Verhoye Annemie Van der Linden Georgios A. Keliris |
| author_sort | Lore M. Peeters |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T23:21:36Z |
| format | Article |
| id | doaj.art-1d227eb58c6941a1ae9ed0baf61f5051 |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-12-12T23:21:36Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-1d227eb58c6941a1ae9ed0baf61f50512022-12-22T00:08:16ZengElsevierNeuroImage1095-95722020-10-01220117088Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivityLore M. Peeters0Rukun Hinz1Jan R. Detrez2Stephan Missault3Winnok H. De Vos4Marleen Verhoye5Annemie Van der Linden6Georgios A. Keliris7Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, BelgiumBio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, BelgiumLaboratory for Cell Biology and Histology, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, BelgiumBio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, BelgiumLaboratory for Cell Biology and Histology, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, BelgiumBio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, BelgiumBio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, BelgiumBio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium; Corresponding author. Bio-Imaging Lab, University of Antwerp, Campus Drie Eiken, Building UC 1.17, Universiteitsplein 1, 2610, Wilrijk, Belgium.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.http://www.sciencedirect.com/science/article/pii/S1053811920305747Designer receptors exclusively activated by designer drugs (DREADDs)Kappa-opioid receptor DREADDs (KORD)Pharmacological functional MRIResting state functional MRINeuronal activityFunctional connectivity |
| spellingShingle | Lore M. Peeters Rukun Hinz Jan R. Detrez Stephan Missault Winnok H. De Vos Marleen Verhoye Annemie Van der Linden Georgios A. Keliris Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity NeuroImage Designer receptors exclusively activated by designer drugs (DREADDs) Kappa-opioid receptor DREADDs (KORD) Pharmacological functional MRI Resting state functional MRI Neuronal activity Functional connectivity |
| title | Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity |
| title_full | Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity |
| title_fullStr | Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity |
| title_full_unstemmed | Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity |
| title_short | Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity |
| title_sort | chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity |
| topic | Designer receptors exclusively activated by designer drugs (DREADDs) Kappa-opioid receptor DREADDs (KORD) Pharmacological functional MRI Resting state functional MRI Neuronal activity Functional connectivity |
| url | http://www.sciencedirect.com/science/article/pii/S1053811920305747 |
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