Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Neurosciences

Language

English (en)

Date of Award

Spring 3-28-2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Timothy E Holy

Abstract

Understanding how sensory systems encode stimuli is a fundamental question of neuroscience. The role of every sensory system is to encode information about the identity and quantity of stimuli in the environment. Primary sensory neurons in the periphery are faced with the task of representing all relevant information for further processing by downstream circuits, ultimately leading to detection, classification and potential response. However, environmental variability potentially alters stimulus properties in non-relevant ways. Here, we address these problems using the mouse accessory olfactory system: AOS) as a model. The AOS is an independent olfactory system possessed by most terrestrial vertebrates, although not humans, and is specialized to detect social cues. It mediates behaviors such as reproduction, aggression, and individual identification. Non-volatile compounds found in urine, including sulfated steroids, are the main source of AOS stimuli. Vomeronasal sensory neurons: VSNs), the primary sensory neurons of the AOS, are located in the base of the nasal cavity, and they detect the identity and quantity of stimuli. However, like other sensory cues, urine is subject to environmental modulation through mechanisms such as evaporation and dilution that affect the concentrations of ligands in non-biologically relevant ways. Ideally, the AOS represents stimuli in ways that are stable across condition.

In the scope of this thesis, I explore how the AOS represents concentration at the levels of the individual neuron, the circuit and the whole animal. Using extracellular recordings of explanted tissue, we characterized how VSNs encode stimuli. VSNs fired predominantly in trains of action potentials with similar structure during spontaneous and stimulus-driven activity. Using pharmacological and genetic tools, we demonstrated that the signal transduction cascade influences the structure of both spontaneous and stimulus-driven activity. Then, we explored the representation of concentration of sulfated steroids by VSNs and the circuit mechanisms by which the AOS can represent concentration information in a manner invariant to environmental uncertainties. We identified ratio-coding as a means for stable concentration representation. The ratio of the concentrations of non-volatile ligands found in urine will not change following urine evaporation or dilution, while the individual concentrations will. This property allows for both insensitivity to changes in absolute concentration and sensitivity to changes in relative concentration. Using extracellular recording and computational modeling, we have demonstrated that VSN activity can be used to robustly encode concentration using ratios. Finally, we attempted to develop a novel behavioral assay to investigate how mice detect AOS stimuli.

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Permanent URL: http://dx.doi.org/10.7936/K7NV9G8J

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