2013/04/20 by Roxana A. Stefanescu, R.G. Shivakeshavan, Stefanescu, Roxana A. +5
Engineering · Neuroscience · #FOS: Biological sciences #Molecular Communication and Nanonetworks #Neural dynamics and brain function #Neurons and Cognition (q-bio.NC) #Neuroscience and Neural Engineering #Photoreceptor and optogenetics research
paper · pdf · doi:10.48550/arxiv.1304.5635
openalex publication_date 2013/04/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Channelrhodopsins-2 (ChR2) are a class of light sensitive proteins that offer\nthe ability to use light stimulation to regulate neural activity with\nmillisecond precision. In order to address the limitations in the efficacy of\nthe wild-type ChR2 (ChRwt) to achieve this objective, new variants of ChR2 that\nexhibit fast mono-exponential photocurrent decay characteristics have been\nrecently developed and validated. In this paper, we investigate whether the\nframework of transition rate model with 4 states, primarily developed to mimic\nthe bi-exponential photocurrent decay kinetics of ChRwt, as opposed to the low\ncomplexity 3 state model, is warranted to mimic the mono-exponential\nphotocurrent decay kinetics of the newly developed fast ChR2 variants: ChETA\n(Gunaydin et al., Nature Neurosci, 13:387-392, 2010) and ChRET/TC (Berndt et\nal., PNAS, 108:7595-7600, 2011). We begin by estimating the parameters for the\n3-state and 4-state models from experimental data on the photocurrent kinetics\nof ChRwt, ChETA and ChRET/TC. We then incorporate these models into a\nfast-spiking interneuron model (Wang and Buzsaki., J Neurosci,\n16:6402-6413,1996) and a hippocampal pyramidal cell model (Golomb et al., J\nNeurophysiol, 96:1912-1926, 2006) and investigate the extent to which the\nexperimentally observed neural response to various optostimulation protocols\ncan be captured by these models. We demonstrate that for all ChR2 variants\ninvestigated, the 4 state model implementation is better able to capture neural\nresponse consistent with experiments across wide range of optostimulation\nprotocol. We conclude by analytically investigating the conditions under which\nthe characteristic specific to the 3-state model, namely the mono-exponential\nphotocurrent decay of the newly developed variants of ChR2, can occurs in the\nframework of the 4-state model.\n