Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors

Abstract

Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71-expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express.

Activity‐dependent formation of the topographic map and the critical period in the development of mammalian olfactory system

“…Additionally, in mosaic analysis, gain of function of the guidance molecules generates duplicated glomeruli, indicating that they can determine the segregation and location of the OSN axons. Later experiments demonstrated that nasal occlusion decreased Kirrel2 expression and increased Kirrel3 expression (Fischl et al, 2014; Molinas et al, 2016; Nakashima et al, 2013). The cell adhesion molecule BIG‐2 (CNTN4) is also identified as an activity‐regulated guidance molecule, which is essential for proper targeting of OSN axons (Kaneko‐Goto et al, 2008) (Figure 1b).…”

Deficits in olfactory system neurogenesis in neurodevelopmental disorders

“…While OSN axons initially coalesce to form supernumerary glomeruli during early development, with some of these glomeruli being heterogeneous, over time these connections refine to produce approximately two homogeneous glomeruli per odorant receptor (Potter et al, 2001; Royal & Key, 1999; Strotmann & Breer, 2006). Unilateral naris occlusion has been shown to delay the refinement of both the number and heterogeneity of glomeruli, highlighting the importance of evoked activity (Cummings & Brunjes, 1994; Farbman et al, 1988; Molinas et al, 2016). Activity also plays a key role in the survival of adult‐born OB interneurons (Mandairon et al, 2006).…”

The influence of olfactory experience on the birthrates of olfactory sensory neurons with specific odorant receptor identities

“…These observations led the investigators to infer that the open‐side and non‐occluded samples had similar transcript profiles (Coppola & Waggener, 2012). Likewise, comparisons between the open‐side OEs from mice that were UNO‐treated via cautery or plug insertion and the OEs of non‐occluded mice have revealed only subtle differences in OSN electrical activity levels (Barber & Coppola, 2015), OSN axon refinement rates (Zou et al, 2004), OSN synaptic remodeling rates (Cheetham et al, 2016), representations of specific OSN subtypes (Molinas et al, 2016; van der Linden et al, 2020), neurogenesis rates of specific subtypes (van der Linden et al, 2020), and levels olfactory marker protein (Waguespack et al, 2005), which has been found to play roles in OSN signal transduction and axon segregation (Albeanu et al, 2018; Buiakova et al, 1996; Lee et al, 2011). On the other hand, prolonged (6 weeks or more) naris occlusion of adult mice that were UNO‐treated via a combination of cautery and suture was found to cause a reduction in OSN quantities within the rostral region of the open side of the OE (Maruniak et al, 1989).…”