AbstractsEngineering

The sense of taste contributes to quality of life and the vital function of discriminating between nutritive and toxic substances. It is intimately associated with appetitive and reward systems as well as homeostatic systems tasked with maintaining nutritional balance and body weight and is subject to widespread modulatory influences associated with digestive and satiety mechanisms including endogenous opioids. Central taste processing is initiated in the rostral nucleus of the solitary tract (rNST). Although there is a significant literature describing fundamental biophysical properties of rNST neurons, their inputs from the solitary tract (ST), and inhibition arising from local interneurons, it is not known how these properties contribute to shaping the gustatory signal as it passes from peripheral afferents to central rNST neurons. In addition, some properties which have been demonstrated in the rNST (such as convergence of ST afferents, short term synaptic depression (STSD) of ST-evoked currents, and inhibition) may interact in ways which are difficult to address using conventional experimental methods. Intrinsic properties and their interactions are central to understanding how the rNST acts to shape the gustatory signal as a relay to higher central structures and to local medullary reflex circuits.The work contained in this dissertation aims to determine the mechanism by which the activation of µ-opioid receptors modulates signal processing in the rNST, and finds that it is primarily a presynaptic inhibition of ST-evoked transmitter release. A second study combines in vitro recording and computational methods, measuring key features of both the ST-rNST synapse and postsynaptic rNST neurons in order to generate a mathematical model of the system. This mathematical model is a tool for understanding the interactions between biophysical properties of the rNST network, exploring the effect of various forms of inhibition on gustatory signal processing, and generating testable predictions regarding modulation, convergence patterns of gustatory afferents, and rNST network configurations. In rNST neurons recorded in vitro, we find that the relationship between input frequency and total ST-evoked current is an increasing, saturating function and that the relationship between applied current and postsynaptic firing rate is characterized by a low threshold and a nearly linear relationship between applied current and firing frequency. When we fit a mathematical model to the in vitro data, we find that convergence and STSD interact to set an appropriate gain between ST input frequencies and rNST output frequencies, that convergence between ST afferents of the same best-stimulus type is required in order to recapitulate the response specificity observed in the rNST in vivo, and that presynaptic inhibition, postsynaptic inhibition, and inhibition by a broadly tuned inhibitory interneuron all function to improve the specificity of the modeled response to gustatory input.