The terminal nerve is an anterior cranial nerve that innervates the lamina propria of the chemosensory epithelia of the nasal cavity. The function of the terminal nerve is ambiguous, but it has been suggested to serve a neuromodulatory role. We tested this hypothesis by exposing olfactory receptor neurons from mudpuppies (Necturus maculosus) to a peptide, gonadotropin releasing hormone (GnRH), that is found in cells and fibers of the terminal nerve. We used voltage-clamped whole-cell recordings to examine the effects of 0.5–50 μmGnRH on voltage-activated currents in olfactory receptor neurons from epithelial slices. We found that GnRH increases the magnitude, but does not alter the kinetics, of a tetrodotoxin-sensitive inward current. This increase in magnitude generally begins 5–10 min after initial exposure to GnRH, is sustained for at least 60 min during GnRH exposure, and recovers to baseline within 5 min after GnRH is washed off. This effect occurred in almost 60% of the total number of olfactory receptor neurons examined and appeared to be seasonal: ∼67% of neurons responded to GnRH during the courtship and mating season, compared with ∼33% during the summer, when the sexes separate. GnRH also appears to alter an outward current in the same cells. Taken together, these data suggest that GnRH increases the excitability of olfactory receptor neurons and that the terminal nerve functions to modulate the odorant sensitivity of olfactory receptor neurons.

As we learn more about the neurobiology of olfaction, it is becoming increasingly clear that olfactory systems of animals in disparate phyla possess many striking features in common. Why? Do these features provide clues about the ways the nervous system processes olfactory information? This might be the case if these commonalities are convergent adaptations that serve similar functions, but similar features can be present in disparate animals for other reasons. For example, similar features may be present because of inheritance from a common ancestor (homology), may represent responses to similar constraints, or may be superficial or reflect strategies used by researchers studying the system. In this paper, I examine four examples of features of olfactory systems in members of different phyla: the presence of odorant binding proteins in the fluid overlying olfactory receptor neurons; the use of G protein-coupled receptors as odorant receptors; the use of a two-step pathway in the transduction of odorant signals; and the presence of glomerular neuropils in the first central target of the axons of olfactory receptor cells. I analyze data from nematodes, arthropods, molluscs, and vertebrates to investigate the phylogenetic distribution of these features, and to try to explain the presence of these features in disparate animals. Phylogenetic analyses indicate that these features are not homologous across phyla. Although these features are often interpreted as convergent adaptations, I find that alternative explanations are difficult to dismiss. In many cases, it seems that olfactory system features that are similar across phyla may reflect both responses to similar constraints and adaptations for similar tasks.

The general features of the olfactory system are remarkably consistent across vertebrates. A phylogenetic analysis of central olfactory projections indicates that at least three distinct olfactory subsystems may be broadly present in vertebrates and that a fourth, the accessory olfactory or vomeronasal system, arose in tetrapods. The origin and function of the vomeronasal system have been the subject of much controversy, but some conclusions can be drawn. The vomeronasal system did not arise as an adaptation to terrestrial life, as indicated by the presence of a vomeronasal system in modern aquatic amphibians and the increasing paleontological evidence that the last common ancestor of amphibians and amniotes was aquatic. The vomeronasal system is involved in both foraging and reproductive behaviors in reptiles and has been shown to be involved in some pheromonally mediated behaviors in mammals. However, among mammals, some pheromonal responses are not mediated by the vomeronasal system, and the possible involvement of the vomeronasal system in other types of behaviors has not yet been investigated. Thus, the relative functions of the olfactory and vomeronasal systems of tetrapods remain unclear. Other hypotheses that features of the olfactory system are specialized for aquatic chemoreception or for pheromone detection are similarly insupportable. For example, the suggestion that members of the olfactory receptor family can be separated into two groups that function for transduction of air-borne or water-borne odorants is contradicted by the presence of both groups in aquatic amphibians and by a phylogenetic analysis of the sequences for these genes. Interestingly, the putative odorant receptors from the vomeronasal epithelium share little sequence similarity with those from the olfactory epithelium, indicating that these receptors may have been independently co-opted from the larger family of seven transmembrane domain receptors for use in odor transduction. A phylogenetic analysis of the distribution of olfactory receptor cell types indicates that microvillar olfactory receptor cells are widespread among vertebrates and are not restricted to aquatic animals or to the vomeronasal epithelium of tetrapods. Previous suggestions that all microvillar receptor cells are specialized for the detection of pheromones are not tenable. Attempts to recognize features of the olfactory system that are common to all vertebrates and might be specialized for the detection of pheromones vs. more general odorants, or for the detection of water-borne vs. air-borne odorants, are not supported by current evidence.

Rough-skinned newts (Taricha granulosa) use tetrodotoxin (TTX) to block voltage-gated sodium (Na_v) channels as a chemical defense against predation. Interestingly, newts exhibit extreme population-level variation in toxicity attributed to a coevolutionary arms race with TTX-resistant predatory snakes, but the source of TTX in newts is unknown. Here, we investigated whether symbiotic bacteria isolated from toxic newts could produce TTX. We characterized the skin-associated microbiota from a toxic and non-toxic population of newts and established pure cultures of isolated bacterial symbionts from toxic newts. We then screened bacterial culture media for TTX using LC-MS/MS and identified TTX-producing bacterial strains from four genera, including Aeromonas, Pseudomonas, Shewanella, and Sphingopyxis. Additionally, we sequenced the Na_v channel gene family in toxic newts and found that newts expressed Na_v channels with modified TTX binding sites, conferring extreme physiological resistance to TTX. This study highlights the complex interactions among adaptive physiology, animal-bacterial symbiosis, and ecological context.