Unique molecular markers for GC-D-expressing olfactory sensory neurons and chemosensory neurons of the Grueneberg ganglion

Abstract

The main olfactory bulb (MOB) is differentiated into subregions based on their innervation by molecularly distinct chemosensory neurons. For example, olfactory sensory neurons (OSNs) that employ a cGMP-mediated transduction cascadeguanylyl-cyclase D-expressing (GC-D+) OSNs of the main olfactory epithelium (MOE) and chemosensory neurons of the Grueneberg ganglion (GGNs) -project to distinct groups of "necklace" glomeruli encircling the caudal MOB. To better understand the unique functionality and neural circuitry of the necklace glomeruli and their associated sensory neurons, we sought to identify additional molecular markers that would differentiate GC-D+ OSNs and GGNs as well as their target glomeruli. We found in mouse that GC-D+ OSNs, but not other MOE OSNs or GGNs, express the neuropeptide CART (cocaine-and amphetamine-regulated transcript). Both GC-D+ OSNs and GGNs, but not other MOE OSNs, express the Ca 2+ /calmodulin-dependent phosphodiesterase Pde1a, which is immunolocalized throughout the dendrites, somata and axons of these neurons. Stronger Pde1a immunolabeling in necklace glomeruli innervated by GGNs than in those innervated by GC-D+ OSNs suggests either greater Pde1a expression in individual GGNs than in GC-D+ OSNs or a difference in sensory neuron innervation density between the two types of necklace glomeruli. Together, the unique molecular signatures of GC-D+ OSNs, GGNs and their MOB targets offer important tools for understanding the processing of chemosensory information by olfactory subsystems associated with the necklace glomeruli.

Olfactory subsystems associated with the necklace glomeruli in rodents

“…Pde2a and Cnga3 are also expressed in GGNs, but not GC-D or Car2 (Fleischer et al 2009;Liu et al 2009;Schmid et al 2010). The neuropeptide CART is not expressed in GGNs (Huang et al 2018).…”

“…Indeed, while Cnga2 null mice show a loss of afferent activity to canonical glomeruli, it is retained to Pde2A+ glomeruli (Baker et al 1999). Instead, GC-D+ OSNs express proteins implicated in cGMPmediated signaling, including the cGMP-stimulated phosphodiesterase Pde2A, the Ca 2+calmodulin stimulated PDE isoform PDE1A and the cGMP-specific CNG channel subunits Cnga3 and Cngb3, in addition to GC-D itself (Bloom et al 2020;Fulle et al 1995;Hu et al 2007;Huang et al 2018;Juilfs et al 1997). Treatment with the cyclic nucleotide analog 8bromo-cGMP increases action potential firing in GC-D+ OSNs (Leinders-Zufall et al 2007), while pharmacologic inhibition or genetic deletion of Cnga3 renders the cells incapable of activation by chemosensory stimuli (Leinders-Zufall et al 2007;Munger et al 2010).…”

Illuminating the terminal nerve: Uncovering the link between GnRH‐1 neuron and olfactory development

“…Transcriptomic analysis of the Prokr2+ pioneer/TN cells revealed an enriched expression of the putative Grueneberg ganglia marker Pde2a (Zhi Huang, 2018), Pcsk1n, Tmem130, and Resp18.…”

Illuminating the Terminal Nerve: Uncovering the Link between GnRH-1 and Olfactory Development

“…Transcriptomic analysis of the Prokr2+ Pioneer/TN cells revealed an enriched expression of the putative Grueneberg ganglia marker Pde2a (Zhi Huang, 2018), Pcsk1n, Tmem130, and Resp18. In addition to these, in the Migratory Prokr2+ cells, we identified the expression of several previously reported antigens for the putative terminal nerve/pioneer neurons, such as Calbindin1 (Fujiwara et al, 1997) (Fig.…”