Michael A. Henson Group

Multiscale Modeling and Analysis of Circadian Rhythm Generation and Synchronization

In mammals, many physiological and behavioral events are subject to well controlled daily oscillations. These rhythms are generated by an internal self-sustained oscillator located in the hypothalamic suprachiasmatic nucleus (SCN). The SCN consists of a broad range of neural subgroups, differentiated according to their neuropeptide content, their afferent and efferent connections with other regions of the brain, and their oscillatory behavior. Circadian rhythmicity is ensured not only by autonomous intracellular mechanisms within individual cells but also by intercellular communication that coordinates these functionally and structurally distinct cell types across the SCN. Vasoactive intestinal polypeptide (VIP) is a critical neuropeptide involved in intercellular communication and the synchronization of circadian rhythm. The neurotransmitter ?-aminobutyric acid (GABA) has also been proposed to involved in synchronization of the SCN network.

The goal of this project is to develop multicellular models based on multiscale descriptions of individual neurons to better understand VIP and GABA mediated intercellular communication within the SCN. A detailed single neuron model that couples circadian gene regulation and electrophysiology was developed to study the modulation of cellular rhythms. Extensive computational studies on the effect of neural network topology and intercellular coupling on circadian rhythm generation and synchronization have been conducted. Our most recent work is focused on developing a multicellular model of the SCN core and shell regions to investigate core-to-shell couplings and differential regulation of circadian signals.

Funding: National Institutes of Health

Student: Ph.D. position available

Collaborator: Frank Doyle (UCSB), Linda Petzold (UCSB) and Erik Herzog (Washington University)

Publications and Recent Presentations:

1. To, T.-L., M. A. Henson, E. D. Herzog and F. J. Doyle III, "A Computational Model for Intercellular Synchronization in the Mammalian Circadian Clock," Biophysical Journal, 92,3792-3803 (2007). [PDF]
2. Vasalou C., E. D. Herzog and M. A. Henson, "Small World Network Models of Intercellular Coupling Predict Enhanced Synchronization in the Suprachiasmatic Nucleus," Journal of Biological Rhythms, 24, 243-254 (2009). [PDF]
3. Vasalou C. and M. A. Henson, "A Multiscale Model to Investigate Circadian Rhythmicity of Pacemaker Neurons in the Suprachiasmatic Nucleus,'' PLOS Computational Biology, 6: e1000706. doi:10.1371/journal.pcbi.1000706 (2010). [PDF]
4. Vasalou, C., E. D. Herzog and M. A. Henson, "A Model for Intercellular Synchronization in Circadian Neural Networks, " Biophysical Journal, 101, 12-20 (2011). [PDF]