UC San Diego

One’s perception of the world is personal. Different people can experience the same sensory stimulus in myriad ways, and the same person can experience the same sensory stimulus differently across time. What factors cause sensory experiences to differ? While daunting, identifying the sources of individualized perception is essential to understanding how the brain functions – to truly understand a circuit, one must understand how inputs are processed. Olfaction, which is essential for many complex mouse behaviors and influenced by both experience and state, is a prime candidate for the study of such variation. While olfactory variation is known to exist, the biological, historical, or technical factors it stems from are not. Here, we find two sources of olfactory variation, one biological and one technical. In the first chapter, we find that pheromone-evoked activity is mediated not by one signal transduction cascade but several. None of the discovered signal transduction cascades are dominant, indicating that signaling heterogeneity is an integral feature in the vomeronasal system. These signal transduction cascades are stimulus-specific, hinting at a substantial utility. The discovery of multiple signaling pathways in the vomeronasal system identifies a new source for biological variation in olfaction. In the second chapter of this thesis, we find that the assay and apparatus used for innate olfactory valence tests affect results’ strengths, timing, and conclusions, indicating that current unstandardized assays introduce substantial technical variation to data. We also show that raw data from these assays are unimpressive, often requiring transformation to become significant. Analysis of tests’ raw data reveals that mice are initially attracted to all stimuli and aversive reactions take minutes to manifest – these data suggest that the currently-used position-as-reaction measure is flawed and needs to be replaced. Uncovering these sources of biological and technical variation poises the neuroscience community to understand how animals make sense of the world around them.