An electric field can polarize a neuron, especially a neuron with elongated dendrites, and thus modify its excitability. In this dissertation, we use computational models and analysis to investigate the effects on neural excitability due to externally applied static electric fields and the extracellular currents generated by a spiking neuron. We apply our results to individual and small networks of neurons. This work has potential implications in the areas of neural prosthetics and therapies to treat a number of neurological conditions such as Depression and Epilepsy. This work also contributes to our understanding of the effects of electric fields endogenous to the brain. We first address the effects of polarization induced by non-weak electric fields on elongated neurons with active dendrites. We find that our model agrees with experimental observation for both weak and strong polarization. For intermediate polarization, we identify novel behavior that should be amenable to experimental verification. Through analysis and modeling, we determine the underlying mechanisms for the observed behavior. Currents that are negligible at weak polarizations and associated with the spiking or bursting phase of a neuron play an important role in the response of a resting neuron to either injected or synaptically generated stimulus. For weak polarizations, small differences in model parameters such as extracellular potassium and rate of current injection yield proportionally small differences in the trajectory of the state variables of the neuron. However, as polarization strength increases the trajectories begin to diverge falling into either a sublinear or superlinear response categories with respect to polarization. We identify the relative strengths of the hyperpolarizing and depolarizing active dendrite currents as a predictor of polarization-dependent excitability. In the second part of the dissertation, we look at localized ephaptic effects due to a single spiking neuron on spike propagation in a chain of synaptically connected neurons. Modeling the extracellular currents using a resistive lattice we observe a non-monotonic relationship between excitability and extracellular resistance. Furthermore, this surprising result is evident for a range of resistances that fall within those estimated using experimentally measured parameters. We define three mechanisms of the localized ephaptic effects; source loading, synaptic coupling and nonsynaptic membrane currents. Through computational experiment and analysis, we are able to analyze these effects as a function of the time between the ephaptic polarization and synaptic input as well as extracellular resistance.
|Commitee:||Barreto, Ernest, Cebral, Juan, Peixoto, Nathalia|
|School:||George Mason University|
|Department:||Computational Sciences and Informatics|
|School Location:||United States -- Virginia|
|Source:||DAI-B 77/07(E), Dissertation Abstracts International|
|Subjects:||Neurosciences, Applied Mathematics, Biophysics|
|Keywords:||Electric fields, Ephaptic effects, Excitability, Pyramidal neurons, Spike timing|
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