Characterization of an olfactory subsystem

Abstract

Mammals encounter a large number of different odor molecules that provide information about their environment. As the primary sense for rodents, many behavioral responses are based on olfactory information. Elucidating the ways that animals make sense of chemical stimuli is a difficult task, a consequence of the diversity of stimulus types and because chemical stimuli communicate disparate information ranging from food quality to reproductive status. The olfactory system uses several subsystems to process chemical stimuli. These subsystems can be defined by the stimuli to which they respond, the receptors and other molecules they express, and the connections they make to the central nervous system. One such subsystem contains sensory neurons that express components of a cGMP-based sensory transduction cascade, including the receptor guanylyl cyclase, GC-D, the cyclic nucleotide-gated channel subunit CNGA3 and the phosphodiesterase PDE2. These neurons send their axons to specialized regions of the caudal main olfactory bulb, the necklace glomeruli. However, little was known about the chemosensitivity, function, or neural connections of this novel olfactory subsystem. This dissertation contains three sets of experiments that aim to illuminate the biological role of this olfactory subsystem. The first set of studies characterizes the anatomy and function of GC-D-expressing neurons. My data, along with that of my collaborators, demonstrate that GC-D-expressing neurons respond to the natriuretic peptides guanylin and uroguanylin, as well as to the natural stimulus, urine, through an excitatory, cGMP-dependent signaling cascade that requires both GC-D and CNGA3. In the second phase of this study, I examined the sensory input and interglomerular connectivity of the necklace glomeruli. Necklace glomeruli exhibit extensive interglomerular connections with other olfactory subsystems and receive heterogeneous sensory innervation. These findings indicate that the necklace glomeruli integrate natriuretic peptide signals in the context of other olfactory information. In the final section of this dissertation, I investigated the potential behaviors mediated by the GC-D neurons and the necklace glomeruli. Efficient pup suckling, maternal anogenital licking, or detection of the natriuretic peptides guanylin and uroguanylin were all ruled out as behaviors mediated by the GC-D neurons and the necklace glomeruli. Together, these studies highlight the unique nature of the GC-D-expressing sensory neurons and the necklace glomeruli as a novel chemosensory subsystem.