Odor representation in the brain: Insights into activity and sex-dependent processes

The main olfactory system (MOS) has the challenging task of detecting and discriminating thousands of structurally dissimilar molecules entering the nose. Most natural odorants are complex mixtures of many different molecules. Yet even in complex mixtures, the MOS can perceive differences in odor quality due to small changes in the proportions of one or a few molecules in the mixture. Adding a layer of complexity, some odorants, such as urine for mice, elicit different behaviors or physiological responses and perhaps different perceptions in males and females. Understanding how these odorants form perceptions and elicit sex-dependent behavioral or physiologic responses is the focus of this thesis. We demonstrate novel aspects to processing olfactory information that depend on both neuronal activity and sex.; The main olfactory bulb (MOB) is the first relay site between neurons in the nose and neurons in the brain. These neurons communicate in specialized structures called glomeruli, which are functional units analogous to somatosensory cortical barrels. For our studies, we examined one subset of the approximately 2000 glomeruli in the MOB, the P2 glomeruli. We demonstrate that the size and number of P2 glomeruli varies in mice housed in cages with different modes of ventilation. Next we show that P2 glomeruli are structurally and functionally asymmetric across domains, which is dependent on neuronal activity. Then we demonstrate that P2 glomeruli in adult male and female mice display sexually dimorphic asymmetries that are activity-dependent. Lastly, we show that brain-derived neurotrophic factor (BDNF) is necessary to support the sexually dimorphic asymmetries of the P2 glomeruli. These results provide evidence that neuronal activity and sex affect asymmetric features of some glomeruli. Our findings are particularly important because, to date, glomeruli only show symmetrical features. Asymmetric features may serve to convey additional information on odor quality important for detecting subtle differences in biologically meaningful sensory stimuli and may be related to sex differences in MOS-mediated behavior. Furthermore, evidence is provided that shows these asymmetric features are maintained by BDNF establishing the first component of the pathway. These data further our understanding of the neural basis for sexually differentiated behaviors.