Computational Modeling of Optogenetic Switching of Neurons

Abstract

Optogenetics has revolutionized neuroscience by controlling neuronal spiking with light with unprecedented spatio-temporal resolution, which is important for a wide range of biomedical applications. In optogenetics, natural light-sensitive proteins, especially microbial rhodopsins, are expressed in neurons to control them with light. Current research is focused on the discovery and design of ultrasensitive, ultrafast, and red-shifted mutants for deep brain stimulation. newlineThe thesis is focused on the formulation of accurate theoretical models of optogenetic mediated neuronal switching that include excitation, inhibition, and bidirectional control. Theoretical models of the photocycle of the recently discovered proteins, such as blue and green light excitable ultrafast Chronos, red-shifted vf-Chrimson, and orange light excitable NpHR have been formulated. The incorporation of the effect of their photoresponse in different neurons, such as hippocampal and neocortical interneurons that have been experimentally reported has also been carried out. The theoretical results are in good agreement with recently reported experimental results and also provide new insights to optimize the optical control of neuronal activity. newlineA major challenge in optogenetics is to achieve low-power, high-frequency, and high-fidelity neural switching. It is, therefore necessary to optimize irradiance and pulse-width and pulse frequency of optical excitation, along with the expression density, for improving temporal fidelity over a wide range of stimulation frequencies. An extensive theoretical analysis has been carried out to determine optimal conditions to achieve low-power and high frequency optogenetic mediated neuronal spiking. newlineThe study is important and useful for designing new experiments with desired spatio-temporal resolution and would prove beneficial for restoration of vision, auditory nerve activity, optical cochlear implants and other neurodegenerative diseases. newline newline