Scent of stem cells: How can neurogenesis make us smell better?

Abstract

Throughout the animal kingdom, olfaction underlies the ability to perceive chemicals in the environment as a fundamental adaptation with a plethora of functions. Unique among senses, olfaction is characterized by the integration of adult born neurons at the level of both the peripheral and central nervous systems. In fact, over the course of life, Neural Stem Cells (NSCs) reside within the peripheral Olfactory Epithelium (OE) and the brain's subventricular zone that generate Olfactory Sensory Neurons (OSNs) and interneurons of the Olfactory Bulb (OB), respectively. Despite this unique hallmark, the role(s) of adult neurogenesis in olfactory function remains elusive. Notably, while the molecular signature and lineage of both peripheral and central NSC are being described with increasing detail and resolution, conflicting evidence about the role of adult born neurons in olfactory sensitivity, discrimination and memory remains. With a currently increasing prevalence in olfactory dysfunctions due to aging populations and infections such as COVID-19, these limited and partly controversial reports highlight the need of a better understanding and more systematic study of this fascinating sensory system. Specifically, here we will address three fundamental questions: What is the role of peripheral adult neurogenesis in sustaining olfactory sensitivity? How can newborn neurons in the brain promote olfactory discrimination and/or memory? And what can we learn from fundamental studies on the biology of olfaction that can be used in the clinical treatment of olfactory dysfunctions?

Keywords: adult neurogenesis; odor discrimination; odor sensitivity; olfaction; olfactory bulb; olfactory epithelium.

FIGURE 1

How can adult neurogenesis promote olfaction? (A) At the level of the peripheral nervous system, adult neurogenesis may respond to olfactory stimuli changing the abundance of specific OSNs (indicated by colors) by (a) changing the maturation or survival of immature OSNs or (b) increasing neurogenesis itself. (B) Effects of enhanced (red lines) relative to basal (gray) brain neurogenesis on olfactory discrimination are modeled based on (a) improved innate ability, (b) learning, or (c) maximal performance. Combinations thereof were not depicted. (C) Olfactory experience may act both in humans and rodents on olfactory neurogenic niches supporting functions such as sensitivity or discrimination. Converse to Bragado Alonso et al. (2019) decrease in neurogenesis and discrimination was reported by Li et al. (2018). Figure created with BioRender.