Bulletin of Mathematical Biology

, Volume 75, Issue 11, pp 2208–2240 | Cite as

Computational Modeling of Channelrhodopsin-2 Photocurrent Characteristics in Relation to Neural Signaling

  • Roxana A. Stefanescu
  • R. G. Shivakeshavan
  • Pramod P. Khargonekar
  • Sachin S. TalathiEmail author
Original Article


Channelrhodopsins-2 (ChR2) are a class of light sensitive proteins that offer the ability to use light stimulation to regulate neural activity with millisecond precision. In order to address the limitations in the efficacy of the wild-type ChR2 (ChRwt) to achieve this objective, new variants of ChR2 that exhibit fast mon-exponential photocurrent decay characteristics have been recently developed and validated. In this paper, we investigate whether the framework of transition rate model with 4 states, primarily developed to mimic the biexponential photocurrent decay kinetics of ChRwt, as opposed to the low complexity 3 state model, is warranted to mimic the mono-exponential photocurrent decay kinetics of the newly developed fast ChR2 variants: ChETA (Gunaydin et al., Nature Neurosci. 13:387–392, 2010) and ChRET/TC (Berndt et al., Proc. Natl. Acad. Sci. 108:7595–7600, 2011). We begin by estimating the parameters of the 3-state and 4-state models from experimental data on the photocurrent kinetics of ChRwt, ChETA, and ChRET/TC. We then incorporate these models into a fast-spiking interneuron model (Wang and Buzsaki, J. Neurosci. 16:6402–6413, 1996) and a hippocampal pyramidal cell model (Golomb et al., J. Neurophysiol. 96:1912–1926, 2006) and investigate the extent to which the experimentally observed neural response to various optostimulation protocols can be captured by these models. We demonstrate that for all ChR2 variants investigated, the 4 state model implementation is better able to capture neural response consistent with experiments across wide range of optostimulation protocol. We conclude by analytically investigating the conditions under which the characteristic specific to the 3-state model, namely the monoexponential photocurrent decay of the newly developed variants of ChR2, can occur in the framework of the 4-state model.


Model Neuron Closed State Neural Response Root Means Square Deviation Hippocampal Pyramidal Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank Lisa Gunaydin and Andre Berndt for sharing their data with us. This research was funded by startup funds to SST; the intramural grant on Computational Biology at the University of Florida; and the Wilder Center of Excellence for Epilepsy Research and the Children’s Miracle Network. P.P.K. was partially supported by the Eckis Professor Endowment at the University of Florida.

Supplementary material

11538_2013_9888_MOESM1_ESM.pdf (408 kb)
(PDF 408 kB)


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Copyright information

© Society for Mathematical Biology 2013

Authors and Affiliations

  • Roxana A. Stefanescu
    • 1
  • R. G. Shivakeshavan
    • 2
  • Pramod P. Khargonekar
    • 3
  • Sachin S. Talathi
    • 1
    • 2
    • 4
    Email author
  1. 1.Department of Pediatrics, Division of NeurologyUniversity of FloridaGainesvilleUSA
  2. 2.Department of Biomedical EngineeringUniversity of FloridaGainesvilleUSA
  3. 3.Department of Electrical EngineeringUniversity of FloridaGainesvilleUSA
  4. 4.Department of NeuroscienceUniversity of FloridaGainesvilleUSA

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