The olfactory bulb is an organized structure well-suited to study the responses of individual neurons in relation to distributed patterns of activity across a neuronal network during processing of sensory information. The spatio-temporal distribution of activity in the bulb depends not only on the pattern of the projections from the epithelium, but also on active mechanisms intrinsic to it. Since mitral/tufted neurons are the main input-output pathway in the bulb, changes in their excitability not only affect output patterns, but also affect the activity of other bulbar neurons. For this reason, elucidation of mechanisms controlling excitability in these cells is critical for understanding how odor information is processed. Complex sequences of depolarization and hyperpolarization characterize mitral/tufted (M/T) cell responses during either odor or electric stimulation. To what degree these patterns arise from synaptic interactions, or from intrinsic membrane properties is not at present known. Voltage sensitive dye and electrophysiological recordings have suggested that facilitatory and long-lasting dendritic depolarization is associated with regenerative Ca2+ currents in M/T dendrites. Synaptic interactions and active membrane properties can regulate spread of activity in dendrites and thereby influence responses not only at the soma but also global patterns of activity throughout the bulbar circuits. Despite the importance of these events, little is known about electrical properties in dendrites. The goal of this project is to examine the relative contributions Of synaptic and intrinsic membrane currents to the spatio-temporal spread of the activity in M/T processes using a combination of electrophysiological and optical recordings. Voltage sensitive dyes win be used to monitor global patterns of bulbar responses at dendritic levels, Ca2+ indicators to assess the contribution of Ca2+ transients in single M/T cells, and intracellular recordings to correlate these events with membrane potential changes at the soma. Ionic and pharmacological manipulations will be used to examine the contributions of intrinsic membrane and synaptic currents to particular responses as well as to examine M/T excitability. The tiger salamander is a good animal model to study M/T cell responses because it permits the use of highly controlled odor stimulation and much anatomical and physiological data have already been gathered. Since distributed patterns of activity appear at an early stage in the olfactory pathway, these studies on the olfactory bulb may reveal the influences of pattern of activity from neighboring neurons on the expression of particular membrane properties. In addition, these analyses should elucidate the contributions of dendritic events to spatio-temporal integration and to the processing of odor stimulus attributes in the olfactory bulb.
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