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 mono-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 bi-exponential 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., PNAS, 108:7595-7600, 2011). We begin by estimating the parameters for 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 mono-exponential
photocurrent decay of the newly developed variants of ChR2, can occurs in the
framework of the 4-state model.Comment: 10 figure
