Purchase this article with an account.
Samuel D. Faught, Olivia J. Walch, Caiping Hu, Daniel B. Forger, Kwoon Y. Wong; Mathematical Modeling of the Electrical Activity of Intrinsically Photosensitive Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4343.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) are mammalian photoreceptors that mediate non-image-forming vision. They control many subconscious physiological processes including pupil resizing, circadian photoentrainment and melatonin secretion. Despite extensive mathematical modeling of retinal neurons, no mathematical models currently exist to predict the electrical activity of ipRGCs. Our preliminary studies aimed to develop a first-generation mathematical model for the electrical activity of these ganglion cells.
Whole-cell recordings were obtained from EGFP-labeled ipRGCs (Ecker et al. 2010 Neuron) in flat-mount mouse retinas. All five types of ipRGCs were studied. Current steps, voltage steps and voltage ramps were applied to analyze spiking patterns and voltage-gated currents. All cells were stained with Lucifer Yellow or Alexa Fluor 488 to reveal their morphologies, and were classified according to dendritic morphology and stratification level. Simulations were performed using Hodgkin-Huxley-type models (e.g. Folhmeister & Miller 1997 J. Neurophysiol.; Forger & Sim 2007 J. Biol. Rhythms) in the Matlab or Neuron environment.
We find that ipRGC electrical activity seems to be closer to the behavior of previously published mathematical models of suprachiasmatic nucleus (SCN) neurons (hypothalamic cells to which the M1-type ipRGCs project) than to previously proposed models of RGC electrical activity. It is also interesting that both SCN neurons and M1 cells show pronounced depolarization block in response to stimulation. Cell morphology can have a large impact on the electrical activity predicted by our models; this could potentially explain some of the differences in behavior we measured in the five different types of ipRGCs. Additionally, our recordings showed that the strength of L- and T-type calcium currents can vary greatly in different ipRGC types. We have started to use modeling to explore how varying these two types of calcium currents change the electrical activity of ipRGCs.
Taken together, these results indicate that mathematical modeling of ipRGCs can play an important role in understanding their function.
This PDF is available to Subscribers Only