Norepinephrine stimulates glycogenolysis in astrocytes to fuel neurons (Coggan et al 2018)

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Accession:262373
"The mechanism of rapid energy supply to the brain, especially to accommodate the heightened metabolic activity of excited states, is not well-understood. We explored the role of glycogen as a fuel source for neuromodulation using the noradrenergic stimulation of glia in a computational model of the neural-glial-vasculature ensemble (NGV). The detection of norepinephrine (NE) by the astrocyte and the coupled cAMP signal are rapid and largely insensitive to the distance of the locus coeruleus projection release sites from the glia, implying a diminished impact for volume transmission in high affinity receptor transduction systems. Glucosyl-conjugated units liberated from glial glycogen by NE-elicited cAMP second messenger transduction winds sequentially through the glycolytic cascade, generating robust increases in NADH and ATP before pyruvate is finally transformed into lactate. This astrocytic lactate is rapidly exported by monocarboxylate transporters to the associated neuron, demonstrating that the astrocyte-to-neuron lactate shuttle activated by glycogenolysis is a likely fuel source for neuromodulation and enhanced neural activity. Altogether, the energy supply for both astrocytes and neurons can be supplied rapidly by glycogenolysis upon neuromodulatory stimulus."
Reference:
1 . Coggan JS, Keller D, Calì C, Lehväslaiho H, Markram H, Schürmann F, Magistretti PJ (2018) Norepinephrine stimulates glycogenolysis in astrocytes to fuel neurons with lactate. PLoS Comput Biol 14:e1006392 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Glia;
Brain Region(s)/Organism:
Cell Type(s): Locus Coeruleus neuron; Astrocyte;
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Volume transmission;
Implementer(s): Coggan, Jay S [jay.coggan at epfl.ch]; Keller, Daniel ;
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CogganEtAl2018
orig
readme.txt
coggan_ngv_new_ModelDB.mod
coggan_ngv_new_ModelDB.hoc
                            
This is the readme for the models associated with the paper:

Coggan JS, Keller D, Calì C, Lehväslaiho H, Markram H, Schürmann F, Magistretti PJ (2018) Norepinephrine stimulates glycogenolysis in astrocytes to fuel neurons with lactate. PLoS Comput Biol 14:e1006392

This code was contributed by JS Coggan.

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