טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentYonatan Weissler
SubjectRealistic Simulation of Neural Excitation Through
Nano-scale Effectsum
DepartmentDepartment of Nanoscience and Nanotechnology
Supervisors Full Professor Shoham Shy
Dr. Brosh Inbar


Abstract

Neural stimulation plays an increasingly important role in the study of brain function and in a growing array of therapeutic interventions. Different modalities can directly excite or suppress neuronal activity in the central nervous system on milliseconds time scale. Several of these modalities are now understood to be mediated by sub-micron and nanoscale effects, including optical stimulation modalities such as optogenetics, Infrared Neural Stimulation (INS), Photo-absorber Induced Neural-thermal Stimulation (PAINTS) and remote stimulation modalities such as ultrasonic neural modulation. These new excitation modalities can potentially provide new neural interfaces with the means of generating and controlling precise and sparse neural activity patterns, similar to those observed in the normally functioning brain.

Ideally, the engineering of the neural interfaces should be supported by computer aided design and simulations. However, because these new modalities are not fully understood and rely on complex spatio-temporal patterning, they are not currently integrated into standard computer simulation tools. In order to bridge this gap we developed the NeuroLab tool, a novel interface between the neuro-simulator NEURON and the general purpose analysis tool MATLAB. By combining these computational tools, NeuroLab is suited for simulating different kinds of stimuli and neural models and for examining complex stimulation patterns at the single cell level.

Next, we developed an array of simulations: the PAINTS and the two-photon optogenetic excitation modalities on three-dimensional morphologically structured neurons and ultrasonic neural modulation on a small scale neural network. These simulations were validated using experimental and stimulation results. Furthermore, the study included a systematic analysis of a large set of computerized single neuron models from a cataloged online database, which allows a robust and comprehensive simulation of the modality on different types of cells.

Interestingly, during the development of an optogenetics simulator, we identified limitations in the ability to adapt the conventional computational model of the light-gated ionic currents to the simulation’s requirements. These led us to propose model modifications which capture the dynamics of the ionic current under different spectral and intensity illumination conditions. Our new modelling approach is suited for red-shifted optogenetic probes and provides new predictions for the spectral response of the ReaChR variant. By combining NeuroLab and the new model, we then developed the first computer simulation for light-scanning two-photon neural excitation. As the new modelling framework is rooted in the experimental studies of the channel’s photocycles, its successful predictions may also help to shed new light and inform our understanding on several aspects of the channelrhodopsins’ biophysics.