Bridging the gap between single receptor type activity and whole‐brain dynamics. (22nd April 2021)

• Record Type: Journal Article
• Authors: Jancke, Dirk; Herlitze, Stefan; Kringelbach, Morten L.; Deco, Gustavo
• Is Part Of: FEBS journal. Volume 289:Number 8(2022)
• Page Start: 2067
• Page End: 2084
• Publication Date: 2021-04-22
• Subjects: 5‐HT1A -- 5‐HT2A -- molecular & cellular neuroscience -- neurotransmitter -- PET -- protein design -- receptor trafficking -- serotonin -- visual cortex -- whole‐brain modelling; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15855
• Languages: English
• ISSNs: 1742-464X

Abstract

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. Abstract : How single neuronal receptor types influence entire brain dynamics remains elusive. We propose a model that combines the brain's anatomical and functional constraints with Michaelis–Menten kinetics at individual receptor sites, exemplified by the serotonergic (5‐HT) system. Further, we show how optogenetic tools can be used for evaluation of our hypotheses in animal experiments. Our approaches may trigger new ways for the diagnosis and treatment of psychiatric disorders associated with malfunction of neurotransmitter systems. ​