Vasalou2010_Pacemaker_Neuron_SCN

Model Identifier
BIOMD0000000246
Short description

This the single cell model from the article:
A multiscale model to investigate circadian rhythmicity of pacemaker neurons in the suprachiasmatic nucleus.
Vasalou C, Henson MA. PLoS Comput Biol 2010 Mar 12;6(3):e1000706. PMID: 20300645 , DOI: 10.1371/journal.pcbi.1000706 ;

Abstract:
The suprachiasmatic nucleus (SCN) of the hypothalamus is a multicellular system that drives daily rhythms in mammalian behavior and physiology. Although the gene regulatory network that produces daily oscillations within individual neurons is well characterized, less is known about the electrophysiology of the SCN cells and how firing rate correlates with circadian gene expression. We developed a firing rate code model to incorporate known electrophysiological properties of SCN pacemaker cells, including circadian dependent changes in membrane voltage and ion conductances. Calcium dynamics were included in the model as the putative link between electrical firing and gene expression. Individual ion currents exhibited oscillatory patterns matching experimental data both in current levels and phase relationships. VIP and GABA neurotransmitters, which encode synaptic signals across the SCN, were found to play critical roles in daily oscillations of membrane excitability and gene expression. Blocking various mechanisms of intracellular calcium accumulation by simulated pharmacological agents (nimodipine, IP3- and ryanodine-blockers) reproduced experimentally observed trends in firing rate dynamics and core-clock gene transcription. The intracellular calcium concentration was shown to regulate diverse circadian processes such as firing frequency, gene expression and system periodicity. The model predicted a direct relationship between firing frequency and gene expression amplitudes, demonstrated the importance of intracellular pathways for single cell behavior and provided a novel multiscale framework which captured characteristics of the SCN at both the electrophysiological and gene regulatory levels.

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To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Format
SBML (L2V4)
Related Publication
  • A multiscale model to investigate circadian rhythmicity of pacemaker neurons in the suprachiasmatic nucleus.
  • Christina Vasalou, Michael A Henson
  • PLoS computational biology , 3/ 2010 , Volume 6 , Issue 3 , pages: e1000706 , PubMed ID: 20300645
Contributors
Submitter of the first revision: Lukas Endler
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modeller: Lukas Endler

Metadata information

is (2 statements)
BioModels Database BIOMD0000000246
BioModels Database MODEL1004080000

isDerivedFrom (5 statements)
PubMed 11316338
BioModels Database BIOMD0000000073
BioModels Database BIOMD0000000074
BioModels Database BIOMD0000000078
BioModels Database BIOMD0000000083

isDescribedBy (1 statement)
PubMed 20300645

hasTaxon (1 statement)
Taxonomy Mammalia

isVersionOf (1 statement)
occursIn (1 statement)
hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model


Curation status
Curated


Connected external resources