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.