CAIMS PIMS Early Career Award: A Detailed Look at How Light Entrains the Circadian Clock

Adam Stinchcombe

A detailed simulation of the circadian (24-hour) timekeeping mechanism can help to address questions related to shift-work, jet lag, and a variety of diseases. The site of the master circadian clock is the suprachiasmatic nucleus (SCN), which consists of 20,000 electrically and chemically coupled neurons. The molecular clock is a transcription-translation feedback loop within each cell that is modelled by a system of ordinary differential equations. On a faster timescale, the electrical activity of these neurons is driven by voltage-gated ion channels, internal calcium dynamics, and synaptic currents, which can also be described by ordinary differential equations. Importantly, the phase of the circadian rhythm in the SCN is entrained to the light-dark cycle. Photic information is relayed to the SCN from M1 intrinsically photosensitive retinal ganglion cells which directly detect light with melanopsin and indirectly via rods and cones. Along with this so-called subconscious vision, traditional vision results from transmembrane currents in the rods and cones. These currents can be detected by electrodes on the surface of the eye. This electroretinography arises from the whole-tissue electrical activity of the retina and can be modelled with the bidomain equations, a system of partial differential equations. Incorporated into this simulation are the detailed ionic current models of the retinal neurons, the phototransduction pathway in the protoreceptors, and the neuronal connectivity of the retina. In this talk, I will discuss my mathematical models of the retina and the suprachiasmatic nucleus, as well as the numerical challenges associated with solving these large and multi-scale differential equations. A combination of experiment, mathematical modelling, and simulation provides insight into light’s role in maintaining circadian rhythms.

 Overview  Program