A novel simulation framework for modelling extracellular recordings in cortical tissue : implementation, validation and application to gamma oscillations in mammals

Abstract

This thesis concerns the simulation of local field potentials (LFPs) from cortical network activity; network gamma oscillations in particular. Alterations in gamma oscillation measurements are observed in many brain disorders. Understanding these measurements in terms of the underlying neuronal activity is crucial for developing effective therapies. Modelling can help to unravel the details of this relationship. We first investigated a reduced compartmental neuron model for use in network simulations. We showed that reduced models containing <10 compartments could reproduce the LFP characteristics of the equivalent full-scale compartmental models to a reasonable degree of accuracy. Next, we created the Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX): a Matlab tool for simulating LFPs in large, spatially organised neuronal networks. We used VERTEX to implement a large-scale neocortical slice model exhibiting gamma frequency oscillations under bath kainate application, an experimental preparation frequently used to investigate properties of gamma oscillations. We built the model based on currently available data on neocortical anatomy. By positioning a virtual electrode grid to match Utah array placement in experiments in vitro, we could make a meaningful direct comparison between simulated and experimentally recorded LFPs. We next investigated the spatial properties of the LFP in more detail, using a smaller model of neocortical layer 2/3. We made several observations about the spatial features of the LFP that shed light on past experimental recordings: how gamma power and coherence decays away from an oscillating region, how layer thickness affects the LFP, which neurons contribute most to the LFP signal, and how the LFP power scales with frequency at different model locations. Finally, we discuss the relevance of our simulation results to experimental neuroscience. Our observations on the dominance of parvalbumin-expressing basket interneuron synapses on the LFP are of particular relevance to epilepsy and schizophrenia: changes in parvalbumin expression have been observed in both disorders. We suggest how our results could inform future experiments and aid in the interpretation of their results.