Afferent sensory activity from canonical olfactory sensory neurons prevents ectopic axonal targeting of phosphodiesterase 2A-expressing neurons

In mice, a vast majority of the olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE) utilize the canonical cAMP mediated signal transduction pathway. A small subset of OSNs in the MOE and Grueneberg ganglia does not express the canonical pathway; instead they express the guanylyl cyclase-D (GC-D) or guanylyl cyclase-G (GC-G) and cGMP pathway for chemical signaling. Whereas the canonical OSNs target to typical glomeruli that occupy most of the glomerular layer in the olfactory bulb, the GC-D- and GC-G-expressing OSNs send axons that terminate in the necklace glomeruli restrictly located in the caudal bulb. It is known that afferent sensory activity plays a critical role in precise axonal targeting to the olfactory bulb. However, whether the canonical neurons play a role to restrict the axons of the GC-expressing neurons to the necklace glomeruli in the posterior olfactory bulb is not known. Using an antibody against PDE2A to visualize the GC-D and GC-G axons we examined whether these axons target normally or ectopically in wild type and cyclic nucleotide-gated channel A2 subunit knock out mice (CNGA2KO). We found that in wild type animals, PDE2A-labeled axons target to the necklace glomeruli and only occasionally project ectopically to regions where canonical glomeruli are located. However, there are more and larger PDE2A+ necklace glomeruli in the knockout than in the WT mice. Using a glomerular mapping program, we found that these ectopic glomeruli are located in regions anterior to and are separate clearly from the necklace glomeruli. Abbreviation: septal organ (SO), Grueneberg ganglion (GG), main olfactory epithelium (MOE), vomeronasal organ (VNO), main olfactory bulb (MOB), olfactory sensory neurons (OSNs), olfactory receptor (OR), cyclic AMP (cAMP), Adenylyl cyclase III (ACIII), cyclic nucleotide gated channel (CNGA2), guanylyl cyclases type D (GC-D), phosphodiesterase (PDE2