Date of Award
Doctor of Philosophy (PhD)
A common challenge across sensory processing modalities is forming meaningful associations between the neural responses and the outside world. These neural representations of the world must then be integrated across different sensory systems contributing to each individuals perceptual experience. While there has been considerable study of sensory representations in the visual system of humans and multiple model organisms, other sensory domains, including olfaction, are less well understood. In this thesis, I set out to better understand the sensory representations of the mouse accessory olfactory system (AOS), a part of the olfactory system. The mouse AOS, our model chemosensory system, comprises peripheral vomeronasal sensory neurons (VSNs), the accessory olfactory bulb (AOB), and downstream effectors. Our work describes the neural representations of multiple sensory inputs in the AOS, specifically the representations of odorants in high dimensional chemical sensory space in the AOB, and how these representations are shaped by interactions within the circuit. Given the complex nature of olfactory chemosensory representations, the features of our model system may give new perspectives on the neural representation of the outside world.
In a neural representation of olfactory information, both the interactions between each receptor and odor compounds as well as the circuit mediated interactions could potentially affect the neural representations of the outside world. The initial neural response comprises component interactions between each receptor and the odor; chemical signals must interact with physical receptors. However, chemosensory processing, such as olfaction, requires interpreting a large variety of potentially overlapping chemical cues from the environment with only a finite number of receptor types. This means that each chemical cue does not necessarily activate only one receptor type or region of the circuit, but rather the cue is likely to be represented by multiple receptor and odor component interactions. Also, the component parts of odors may be processed differently when presented in isolation versus in a more complex mixture, thus allowing the response to a particular odor to vary with chemical context. Moreover, once these component representations exist, interactions within the neural circuit may further shape these responses. For example, one might expect component parts of a complex odor to specifically inhibit other component parts. In the case of the accessory olfactory system this inhibition could be at the receptor level or at the level of the sensory representation in the accessory olfactory bulb (AOB).
In Chapter 3, I describe the overall organization of chemosensory representations in the accessory olfactory bulb (AOB), which is found to be a modular map in which the primary associations of functional sensory responses are spatially organized relative to one another. I find these primary associations are condensations of the first order sensory neuron axon terminals, which form population response pooling structures called glomeruli. In these glomeruli, similar response types from those sensory neurons expressing one of the approximately 300 receptor types in the vomeronasal organ (VNO) co-converge. One purpose of converging inputs of neurons expressing the same receptor is likely to minimize noise, and I demonstrate that pooling of like receptor responses into glomeruli does increase neural signal relative to noise. However, I also observed a modular organization among and between glomeruli in which certain types or patterns of chemosensory responses are always spatially adjacent to one another, while others are much farther apart than would be expected by chance. I found this spatial modularity for both ethological stimuli (urine collected from conspecifics with widely divergent physiological endocrine status) and individual sulfated steroids.
In Chapter 4, I explore the consequences of changing sensory context, specifically the presentation of multiple compounds, and the role that inhibition plays in the neural representation of the sensory stimuli. First, I tested whether the circuit responds differently to demands to represent a single odor than to demands to represent multiple odors by using odors that activate glomeruli both inside and outside of modules. I found that responses to mixtures rapidly diverge from the responses of individual component parts. Moreover, there was an effect of inhibition in modulating the response to preferred stimuli in all glomeruli. However, initial analysis of one type of pregnanolone responsive glomeruli demonstrated that the divergent response to mixtures in this type of glomerulus was not mediated by inhibition at the glomerular level, but was rather attributable to bottom-up effects from the interactions of multiple ligands with chemosensory receptors in the VNO. Nonetheless, I also demonstrated that in the AOB, the axon terminals of the same sensory neurons (glomeruli) are organized into modules that allow for feedback inhibition. Significant ionotropic glutamate receptor signal modulation was observed within modules, demonstrating that there are inhibition mediated effects in the representation of complex mixtures when glomeruli are co-locally arranged. Specifically, at both the level of the VSNs and also in AOB glomeruli, the response to allopregnanolone sulfate is inhibited by co-presentation with estradiol sulfate. This both significantly increases the relative representation of estradiol sulfate and shifts representation of allopregnanolone primarily within modules. These types of context dependent interactions depend on the spatial organization described in Chapter 3 as well as mixture context, and have the potential to optimize the representation of some chemical cues in a context specific manner.
Chair and Committee
Timothy E. Holy
Paul A. Gray, Daniel Kerschensteiner, Steven J. Mennerick, Baranidharan Raman,
Hammen, Gary Francis, "The Murine Accessory Olfactory Bulb as a Model Chemosensory System: Experimental and Computational Analysis of Chemosensory Representations" (2016). Arts & Sciences Electronic Theses and Dissertations. 793.