Jancke, DirkHerlitze, StefanKringelbach, Morten L.Deco, Gustavo2021-05-062021-05-062022Jancke D, Herlitze S, Kringelbach ML, Deco G. Bridging the gap between single receptor type activity and whole-brain dynamics. FEBS J. 2022;289(8):2067-84. DOI: 10.1111/febs.158551742-464Xhttp://hdl.handle.net/10230/47340What 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.application/pdfeng© 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf ofFederation of European Biochemical SocietiesThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License https://creativecommons.org/licenses/by-nc/4.0/, which permits use,distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposesinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1111/febs.158555-HT1A5-HT2AMolecular & cellular neuroscienceNeurotransmitterPETProtein designReceptor traffickingSerotoninVisual cortexWhole-brain modellinginfo:eu-repo/semantics/openAccess