Plateau Potential Fluctuations and Intrinsic Membrane Noise

This thesis focuses on subthreshold membrane potential fluctuations in the plateau potentials of bistable neurons. Research involved with plateau potentials typically finds one of the resting membrane potentials to be more susceptible to voltage fluctuations. This difference in the amplitude of the membrane potential fluctuations is most often attributed to the voltage-dependent membrane conductance. Occasionally, however, the typically quieter resting membrane potential exhibits larger voltage fluctuations than the expected one. It has been proposed that this increased membrane potential noise is the result of the stochastic gating of the voltage-gated ion channels. In this thesis, we use a simple bistable neuron model to show that the increased intrinsic membrane noise in the quieter resting membrane potential is most likely not caused by the random gating of the ion channels

Cellular And Synaptic Mechanisms That Underlie Eupnea And Sigh Rhythms For Breathing Behavior In Mice

Breathing is a lifelong activity that involves the coordination of several rhythmic behaviors. This dissertation investigates the neural origins of two of these breathing rhythms: eupnea and sighing. Eupnea, or regular unlabored breathing, occurs on the order of seconds and serves to drive the exchange of oxygen and carbon dioxide between the circulatory system and the environment. Sighs, deep breaths that are typically 2-5 times the volume of a eupneic breath, occur on the order of minutes and are critical in maintaining pulmonary function. Understanding how these rhythms are generated on a cellular and synaptic level is an essential step in preventing numerous pathologies, such as sudden infant death syndrome, and respiratory depression and failure as a consequence of opioids in a clinical setting or as drugs of abuse. First, we uncover the cellular and synaptic mechanisms that couple these two rhythms using electrophysiology and an in vitro breathing model from neonatal mice. Next, using mathematical modeling techniques, we explore how interconnectivity of the neural circuitry may drive the eupnea rhythm. Finally, we layout and test a novel framework for how intracellular calcium oscillations drive the sigh rhythm using a combination of electrophysiology and an in vitro breathing model combined with mathematical modeling. Unraveling the mechanisms that generate the eupnea and sigh rhythms reveals deeper insights into rhythms throughout the brain