Characterization of an Unusual Collection of Olfactory Neurons in the Nose

Abstract

We have used a combination of histochemical, electrophysiological, and behavioral approaches to study signal transduction, membrane biophysics, and chemosensory function in the neurons of the mouse Grueneberg ganglion (GG) olfactory subsystem. The GG is a recently appreciated collection of ~1,000 clustered primary olfactory neurons located at the anterior tip of the mammalian nasal cavity. Despite their far-forward position, GG neurons are fully trapped beneath a keratinized epithelium and are wrapped by glial cells. This raises the question of how they contribute to the sense of smell. We found that GG neurons have key components of cGMP signal transduction pathway and are molecularly similar to GC-D neurons, which project to the enigmatic necklace glomeruli in the olfactory bulb. In electrophysiological analyses, individual GG neurons spontaneously discharged action potentials in one of three distinct temporal patterns that were stable for >20 min. An auxiliary fast-inactivating Na+ current accounted for the various discharge patterns in computer simulations of the neuronal ionic currents. Despite differences in baseline activity, the majority of GG neurons responded to specific mammalian pheromones. In behavioral experiments, we found that the weaning of adolescent mice induced GG activity; however, the effects did not depend on ambient temperature or the presence of other animals. Because GG neurons reside on a dense vascular bed, have specialized access to serum contents, and directly responded to pressure ejections of serum, their activity can likely be modulated by internally circulating hormones or proteins associated with specific physiological states such as stress. Taken together, our results demonstrate unusual molecular and functional aspects of a morphologically and anatomically atypical olfactory nerve.