A multiscale approach to analyze circadian rhythms (Vasalou & Henson, 2010) (CellML)

" ... We developed a firing rate code model to incorporate known electrophysiological properties of SCN (suprachiasmatic nucleus) 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."

Model Type: Neuron or other electrically excitable cell

Cell Type(s): Suprachiasmatic nucleus (SCN) neuron; Abstract rate-based neuron

Currents: I Calcium; I Sodium; I Potassium; I K,Ca

Receptors: IP3; GabaA; AMPA; NMDA

Transmitters: Gaba; Glutamate

Model Concept(s): Circadian Rhythms; Action Potentials; Calcium dynamics; Temporal Pattern Generation; Activity Patterns; Oscillations; Reaction-diffusion; Signaling pathways

Simulation Environment: CellML (web link to model)


Vasalou C, Henson MA. (2010). A multiscale model to investigate circadian rhythmicity of pacemaker neurons in the suprachiasmatic nucleus. PLoS computational biology. 6 [PubMed]

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