State-dependent sculpting of olfactory sensory neurons is attributed to sensory enrichment, odor deprivation, and aging

Abstract

Gene-targeted deletion of the predominant Shaker potassium channel, Kv1.3, in the mitral cells of the olfactory bulb, decreases the number of presynaptic, odorant receptor (OR)-identified olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE) and alters the nature of their postsynaptic connections to mitral cell targets. The current study examined whether OSN density was state-dependent by examining the impact of 1) odor enrichment, 2) sensory deprivation, and 3) aging upon the number of P2- or M72-expressing neurons. Histological approaches were used to quantify the number of OSNs across entire epithelia for wildtype (WT) vs. Kv1.3-null (KO) mice bred onto an ORtauLacZ reporter background. Following either odor-enrichment or early unilateral naris-occlusion, the number of M72-expressing OSNs was significantly decreased in WT mice, but was unchanged in KO animals. Following naris-occlusion, the number of P2-expressing OSNs was decreased regardless of genotype. Animals that were reared to 2 years of age demonstrated loss of both P2- and M72-expressing OSNs in WT mice and a concomitant loss of only M72-expressing neurons in KO mice. These findings suggest that voltage-gated activity of the mitral cells is important for OSN plasticity, and can prevent neuronal loss via sensory- and OR-dependent mechanisms.

Activity-Dependent Modulation of Odorant Receptor Gene Expression in the Mouse Olfactory Epithelium

“…To fully understand the expression level/pattern changes of a single gene, it is essential to employ multiple, complementary approaches. By examining genetically labeled OSNs in P2-IRES-tauLaz mice, two groups reported that sensory deprivation significantly reduced the number of P2 cells [24], [46], which is confirmed by our in situ hybridization data. It is worth noting that both in situ hybridization and microarrays examine the mRNA expression, and more studies would be required to understand how OR protein expression is modulated.…”

A non-canonical di-acidic signal at the C-terminal of Kv1.3 determines anterograde trafficking and surface expression

“…Because Kv1.3 is important in sensory neurons (Rivera et al, 2005;Cavallin et al, 2010;Gazula et al, 2010) and leukocyte physiology (Vicente et al, 2003;Cahalan and Chandy, 2009) we analyzed the di-acidic E483/484 in neurons and lymphocytes. Rat embryo hippocampal neurons and Jurkat T-lymphocytes were transfected with Kv1.3wt and Kv1.3(I483/484).…”

“…In this context, the Kv1.3 channel participates in the activity of sensory neurons and also controls the activation and proliferation of leukocytes (Vicente et al, 2003;Rivera et al, 2005;Cahalan and Chandy, 2009;Cavallin et al, 2010;Gazula et al, 2010). Therefore, Kv1.3 is considered to be a fundamental pharmacological target for diseases related to the nervous and immune systems (Koeberle and Schlichter, 2010;Villalonga et al, 2010;Conforti, 2012).…”

Aging in the olfactory system

“…Custom microarrays, PCR and in situ analyses show individual variability in OR gene expression with peaks occurring between mouse postnatal day 14 and day 60, followed by steep declines for some receptors during aging [12,28,29]. Because the sensitivity of the sensory neurons that continue to express ORs in aged mice appears comparable to younger mice, it seems plausible that receptor copy number for individual cells is not affected during aging [30].…”