Mechanisms of frequency-entrainment in neuromodulated, synaptically driven pacing and bursting cells
Demir, Semahat Siddika
Clark, John W., Jr.
Doctor of Philosophy
The development of quantitative models that describe how neural inputs control the electrophysiological behavior of two cellular oscillators is presented. These cellular oscillators are a spontaneously beating mammalian cardiac cell (the sinoatrial node (SAN) cell of the rabbit heart) and a well-known endogenously bursting neuron (neuron R15 cell from the abdominal ganglion in Aplysia). The models representing the SAN cell and the R15 cell have two major components: a Hodgkin-Huxley type membrane model and a fluid compartment model. Each membrane model consists of the ionic membrane currents, membrane pumps and the exchanger. The fluid compartment model describes the changes for the ions inside and outside the cell. The neuromodulatory effects of the neurotransmitters used in the SAN cell and the R15 cell are modeled in the membrane and fluid compartments in detail consistent with available experimental data. These neuromodulatory effects resulting from single neural inputs are investigated by transient phase sensitivity analysis and are presented in terms of phase response curves (PRCs). Moreover, the effects due to the periodic neural stimulation are analyzed by steady-state entrainment curves. Even though, there are differences in the two biological oscillators studied (SAN and R15 cells), our simulations show that they share many qualitative and quantitative features in their phase sensitivity to input stimuli. This dissertation provides a better understanding of the requirements for the control of a biological oscillator since the study deals with quantitative cell models that permit the investigation of basic mechanisms (currents, concentrations, etc.) underlying the phenomena of phase sensitivity and entrainment in two cells that are representative of the range of complexity in biological oscillators.
Biomedical engineering; Electronics; Electrical engineering