Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs.

Abstract

In mammals, olfactory stimuli are detected by sensory neurons at two distinct sites: the olfactory epithelium (OE) of the nasal cavity and the neuroepithelium of the vomeronasal organ (VNO). While the OE can detect volatile chemicals released from numerous sources, the VNO appears to be specialized to detect pheromones that are emitted by other animals and that convey information of behavioral or physiological importance. The Communication among mammals via chemical messengers known as pheromones may play important roles in a variety of social interactions, especially those associated with reproduction (1-4). Pheromones present in urine or vaginal secretions have been implicated in such effects as the initiation of copulatory behavior in male hamsters and alterations in reproductive state in mice, including acceleration or suppression of puberty and block of pregnancy. The accessory olfactory system, which originates in the sensory neuroepithelium of the vomeronasal organ (VNO), is thought to be specialized to detect pheromones (1-4).In rodents, the VNO is a cartilage-encased tubular structure, which is located at the base of the nasal septum and opens into the nasal cavity via a single duct. Molecules dissolved in nasal mucus are pumped into the VNO lumen by changes in VNO blood volume (5). Like the olfactory epithelium (OE) of the nasal cavity, which detects volatile odorants as well as some pheromones, the VNO neuroepithelium contains sensory neurons that project axons to the olfactory bulb of the brain. However, the pathways followed by sensory information that enters the olfactory system through the VNO and OE, the "accessory" and "main" olfactory pathways, respectively, are distinct and remain separate at all levels of the nervous system (6). OE-derived signals ultimately reach multiple brain regions, including the frontal cortex, which is thought to mediate the conscious perception of odors. In contrast, VNO-derivedThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. signals are targeted to hypothalamic structures implicated in reproductive physiology and behavior (7,8).The neuroepithelium of the VNO is derived embryologically as an evagination from the developing OE and resembles the OE morphologically (9). VNO and OE neurons are both highly unusual among neurons in that they are short-lived and are replaced from a local stem cell population throughout life (10, 11). In addition, both express olfactory marker protein (OMP) (12) and both are bipolar cells that extend fine processes (cilia or microvilli) into the external environment and project axons to the olfactory bulb of the brain (1, 6, 11). These similarities have suggested that neurons in the OE and VNO might use the same mechanisms, perhaps even the same molecules, to transduce sensory stimuli.Very little is known about sensory transduction in the VNO. However, extensive studies of s...

Olfactory mucosa-expressed organic anion transporter, Oat6, manifests high affinity interactions with odorant organic anions

“…Figure 2 demonstrates that Oat6 mRNA is present in total RNA extracts of microdissected epithelia from both mouse MOE and VNO, but not in a comparable amount of RNA from individual olfactory neurons laser-captured from either MOE (three representative samples are shown of a total of 18 MOE neurons) or VNO (three of a total of 6 neurons). In the same samples, expression of β3-tubulin was readily detected, indicating cDNA integrity, as was expression of OMP, indicating neuronal cell identity [13]. These data suggest that Oat6 is expressed in non-neuronal cells of olfactory tissue (possibly epithelial and/or other supporting cells immediately adjacent to neurons).…”

Importance of the CNGA4 channel gene for odor discrimination and adaptation in behaving mice

“…CNGA4 mRNA expression has been reported in sensory neurons of the vomeronasal organ (28), but the functional relevance of this result is not yet clear, especially because cyclic nucleotides fail to activate a conductance in vomeronasal neurons (29). Given the role of the vomeronasal organ in modulation of sexual and social behaviors (30)(31)(32), interpretation of the performance in the behavioral tests used here should not be complicated by a potential function for CNGA4 in the vomeronasal organ.…”

Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

“…Cnga2 is expressed in the olfactory sensory neurons (OSNs) and brain (21,22). Cnga2 knockout mice have severely impaired sniffing behavior, and most of the mutant mice die within 1-2 d of birth (23).…”