Malik, Naveed A. (2011) Frequency-dependent response of neurons to oscillating electric fields. PhD thesis, University of Warwick.

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Abstract

Neuronal interactions with electric fields depend on the biophysical properties of the
neuronal membrane as well as the geometry of the cell relative to the field vector.
Biophysically detailed modeling of these spatial effects is central to understanding
neuron-to-neuron electrical (ephaptic) interactions as well as how externally applied
electrical fields, such as radio-frequency radiation from wireless devices or therapeutic
Deep Brain Stimulation (DBS), interact with neurons. Here we examine in detail the
shape-dependent response properties of cells in oscillating electrical fields by solving
Maxwell's equations for geometrically extended neurons.
Early modeling for compact (spherical) cells in alternating fields predicts a
smaller effective membrane time constant for the field-cell system compared to direct
current injection via whole-cell patch clamp. This result, predicting that cells should
respond strongly to field oscillations in the kHz range, was verified later in vitro for
murine myeloma cells. However, recent experiments on CA3 pyramidal cells (highly
elongated neurons) in the hippocampus do not exhibit this high frequency response.
In this thesis we examine the implications of modeling full two-way coupling between
three-dimensional cylindrical neurons and the extracellular field utilizing three different
methodologies, namely: cable equation, finite-difference and finite-element. Our
modeling demonstrates that the electrotonic length and orientation of the cell to the
field are key determinants of the neuronal response to oscillating fields. This explains
the experimentally observed absence of the high frequency response for pyramidal
neurons when the applied field direction is oriented along their dendritic axis. Additionally,
we developed biophysically detailed models of neuronal membranes with
quasi-active electrical properties stemming from voltage-gated currents. These are
known to lead to resonances at characteristic frequencies in the case of current injection
via whole-cell patch clamp. Interestingly, in the field-cell system, the resonance
was masked in compact, spherical neurons but recovered in elongated neurons.
Utilizing our cable and finite-element models, we investigate the effect of
point-source stimulation on cylindrical neurons and find a novel type of "passive
resonance" not reported before in the literature. We further extend our modeling by
incorporating Hodgkin Huxley channels in to the membrane and construct a fully
active, spiking model of a neuron, fully coupled to the applied electric fields. We
then go on to embed the neuron in to an array of cells to validate our results at the
tissue-level.
These findings delineate the relationship between neuron shape, orientation
and susceptibility to high frequency electric fields, with implications for DBS efficacy,
ephaptic coupling in networks and the filtering properties of cortical tissue.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QC Physics Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Neurons, Electric fields -- Physiological effect, Biophysics -- Mathematical models, Cell physiology, Brain stimulation
Official Date:	August 2011
Dates:	Date Event August 2011 Submitted
Institution:	University of Warwick
Theses Department:	Molecular Organisation and Assembly in Cells ; Warwick Systems Biology Centre
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Richardson, Magnus J. E.
Sponsors:	Engineering and Physical Sciences Research Council (EPSRC)
Extent:	xxxiii, 159 leaves : illustrations, charts.
Language:	eng

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