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  Bridging the gap between single receptor type activity and whole‐brain dynamics

Jancke, D., Herlitze, S., Kringelbach, M. L., & Deco, G. (2021). Bridging the gap between single receptor type activity and whole‐brain dynamics. The FEBS Journal. doi:10.1111/febs.15855.

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Jancke, Dirk1, 2, Author
Herlitze, Stefan3, Author
Kringelbach, Morten L.4, 5, 6, 7, Author
Deco, Gustavo8, 9, 10, 11, Author              
1Optical Imaging Group, Institute for Neuroinformatics, Ruhr University, Bochum, Germany, ou_persistent22              
2International Graduate School of Neuroscience (IGSN), Ruhr University, Bochum, Germany, ou_persistent22              
3Department of General Zoology and Neurobiology, Ruhr University, Bochum, Germany, ou_persistent22              
4Department of Psychiatry, University of Oxford, United Kingdom, ou_persistent22              
5Center for Music in the Brain, Aarhus University, Denmark, ou_persistent22              
6ICVS - Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal, ou_persistent22              
7Centre for Eudaimonia and Human Flourishing, University of Oxford, United Kingdom , ou_persistent22              
8Computational Neuroscience Group, Department of Information and Communication Technologies, Center for Brain and Cognition, University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
9Catalan Institution for Research and Advanced Studies (ICREA), University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
10Department Neuropsychology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634551              
11School of Psychological Sciences, Monash University, Melbourne, Australia, ou_persistent22              


Free keywords: 5-HT1A; 5-HT2A; PET; Molecular & cellular neuroscience; Neurotransmitter; Protein design; Receptor trafficking; Serotonin; Visual cortex; Whole-brain modelling
 Abstract: What is the effect of activating a single modulatory neuronal receptor type on entire brain network dynamics? Can such effect be isolated at all? These are important questions because characterizing elementary neuronal processes that influence network activity across the given anatomical backbone is fundamental to guide theories of brain function. Here, we introduce the concept of the cortical ‘receptome’ taking into account the distribution and densities of expression of different modulatory receptor types across the brain's anatomical connectivity matrix. By modelling whole‐brain dynamics in silico, we suggest a bidirectional coupling between modulatory neurotransmission and neuronal connectivity hardware exemplified by the impact of single serotonergic (5‐HT) receptor types on cortical dynamics. As experimental support of this concept, we show how optogenetic tools enable specific activation of a single 5‐HT receptor type across the cortex as well as in vivo measurement of its distinct effects on cortical processing. Altogether, we demonstrate how the structural neuronal connectivity backbone and its modulation by a single neurotransmitter system allow access to a rich repertoire of different brain states that are fundamental for flexible behaviour. We further propose that irregular receptor expression patterns—genetically predisposed or acquired during a lifetime—may predispose for neuropsychiatric disorders like addiction, depression and anxiety along with distinct changes in brain state. Our long‐term vision is that such diseases could be treated through rationally targeted therapeutic interventions of high specificity to eventually recover natural transitions of brain states.


Language(s): eng - English
 Dates: 2021-03-152021-01-142021-03-312021-04-22
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1111/febs.15855
Other: online ahead of print
PMID: 33797854
 Degree: -



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Project name : -
Grant ID : 001‐P‐001682
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Funding organization : CECH The Emerging Human Brain Cluster
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Grant ID : 945539
Funding program : HBP SGA3 Human Brain Project
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Project name : -
Grant ID : 860563
Funding program : Horizon 2020 Framework Programme
Funding organization : -
Project name : -
Grant ID : JA 945/3‐1, SL 185/1‐1
Funding program : -
Funding organization : German Israeli Project Cooperation (DIP)
Project name : -
Grant ID : HE 2471/12‐1, HE 2471/18‐1, SFB 1280 ‐ 316803389, JA 945/4‐1, JA 945/5‐1, project number 122679504 ‐ SFB 874, MA 5806/1‐2, MA 5806/2‐1
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft
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Grant ID : 101017716
Funding program : H2020 Future and Emerging Technologies
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Project name : Brain‐Connects: Brain Connectivity during Stroke Recovery and Rehabilitation
Grant ID : 201725.33
Funding program : -
Funding organization : Fundacio La Marato TV3
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Grant ID : 2017 SGR 1545
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Funding organization : Catalan Agency for Management of University and Research Grants (AGAUR)
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Grant ID : PCI2018‐09, PID2019‐105772GB‐I00
Funding program : -
Funding organization : Ministerio de Ciencia e Innovación

Source 1

Title: The FEBS Journal
  Other : The Federation if European Biochemical Societies Journal
Source Genre: Journal
Publ. Info: Wiley-Blackwell
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1742-464X
CoNE: https://pure.mpg.de/cone/journals/resource/954925398485