brainsci-12-00728-v4.pdf 2,79MB
1000 Titel
  • Spike-Dependent Dynamic Partitioning of the Locus Coeruleus Network through Noradrenergic Volume Release in a Simulation of the Nucleus Core
1000 Autor/in
  1. Baral, Shristi |
  2. Hosseini, Hassan |
  3. More, Kaushik |
  4. Fabrin, Thomaz |
  5. Braun, Jochen |
  6. Prigge, Matthias |
1000 Erscheinungsjahr 2022
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2022-06-01
1000 Erschienen in
1000 Quellenangabe
  • 12(6):728
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2022
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Ergänzendes Material
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The Locus coeruleus (LC) modulates various neuronal circuits throughout the brain. Its unique architectural organization encompasses a net of axonal innervation that spans the entire brain, while its somatic core is highly compact. Recent research revealed an unexpected cellular input specificity within the nucleus that can give rise to various network states that either broadcast norepinephrine signals throughout the brain or pointedly modulate specific brain areas. Such adaptive input-output functions likely surpass our existing network models that build upon a given synaptic wiring configuration between neurons. As the distances between noradrenergic neurons in the core of the LC are unusually small, neighboring neurons could theoretically impact each other via volume transmission of NE. We therefore set out to investigate if such interaction could be mediated through noradrenergic alpha2-receptors in a spiking neuron model of the LC. We validated our model of LC neurons through comparison with experimental patch-clamp data and identified key variables that impact alpha2-mediated inhibition of neighboring LC neurons. Our simulation confirmed a reliable autoinhibition of LC neurons after episodes of high neuronal activity that continue even after neuronal activity subsided. Additionally, dendro-somatic synapses inhibited spontaneous spiking in the somatic compartment of connected neurons in our model. We determined the exact position of hundreds of LC neurons in the mouse brain stem via a tissue clearing approach and, based on this, further determined that 25 percent of noradrenergic neurons have a neighboring LC neuron within less than a 25-micrometer radius. By modeling NE diffusion, we estimated that more than 15 percent of the alpha2-adrenergic receptors fraction can bind NE within such a diffusion radius. Our spiking neuron model of LC neurons predicts that repeated or long-lasting episodes of high neuronal activity induce partitioning of the gross LC network and reduce the spike rate in neighboring neurons at distances smaller than 25 μm. As these volume-mediating neighboring effects are challenging to test with the current methodology, our findings can guide future experimental approaches to test this phenomenon and its physiological consequences.
1000 Sacherschließung
lokal alpha2-adrenergic receptors
lokal Locus coeruleus
lokal non-synaptic connectivity
lokal volume diffusion
lokal noradrenaline
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 (Academic) Editor
1000 Label
1000 Förderer
  1. Leibniz-Gemeinschaft |
  2. Center for Behavioral Brain Sciences |
1000 Fördernummer
  1. J28/2017 SAW
  2. -
1000 Förderprogramm
  1. Leibniz Best Minds program
  2. ERFE-program 2016–2022 NeuroNetworks
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Leibniz-Gemeinschaft |
    1000 Förderprogramm Leibniz Best Minds program
    1000 Fördernummer J28/2017 SAW
  2. 1000 joinedFunding-child
    1000 Förderer Center for Behavioral Brain Sciences |
    1000 Förderprogramm ERFE-program 2016–2022 NeuroNetworks
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6434055.rdf
1000 Erstellt am 2022-06-29T13:29:54.667+0200
1000 Erstellt von 242
1000 beschreibt frl:6434055
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Mon Aug 01 07:20:19 CEST 2022
1000 Objekt bearb. Mon Aug 01 07:20:03 CEST 2022
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