Developing and maintaining a nose-to-brain map of odorant identity

Abstract

Olfactory sensory neurons (OSNs) in the olfactory epithelium of the nose transduce chemical odorant stimuli into electrical signals. These signals are then sent to the OSNs' target structure in the brain, the main olfactory bulb (OB), which performs the initial stages of sensory processing in olfaction. The projection of OSNs to the OB is highly organized in a chemospatial map, whereby axon terminals from OSNs expressing the same odorant receptor (OR) coalesce into individual spherical structures known as glomeruli. This nose-to-brain map of odorant identity is built from late embryonic development to early postnatal life, through a complex combination of genetically encoded, OR-dependent and activity-dependent mechanisms. It must then be actively maintained throughout adulthood as OSNs experience turnover due to external insult and ongoing neurogenesis. Our review describes and discusses these two distinct and crucial processes in olfaction, focusing on the known mechanisms that first establish and then maintain chemospatial order in the mammalian OSN-to-OB projection.

The role of a ciliary GTPase in the regulation of neuronal maturation of olfactory sensory neurons

“…iOSNs then proceed to become mature OSNs (mOSNs), which undergo multi-ciliogenesis and establish synaptic connections in glomeruli in the OB ( Liberia et al, 2019 ; Rodriguez-Gil et al, 2015 ). Although tremendous effort has been placed in detailing the timing of crucial biological processes during the maturation of OSNs ( Kondo et al, 2010 ; Nickell et al, 2012 ; Rodriguez-Gil et al, 2015 ; Coleman et al, 2017 ; Fletcher et al, 2017 ; Liberia et al, 2019 ; McClintock et al, 2020 ; Wang et al, 2017 ; Kurian et al, 2021 ; Dorrego-Rivas and Grubb, 2022 ), little is understood about the signaling mechanisms responsible for their maturation. Interestingly, there is evidence that neuronal primary cilia, known as ‘signaling antennas’, play crucial roles in the formation and maturation of neurons ( Youn and Han, 2018 ; Han et al, 2008 ) and the regulation of the early patterning of another neuronal tissue, the neural tube ( Caspary et al, 2007 ).…”

In mice, discrete odors can selectively promote the neurogenesis of sensory neuron subtypes that they stimulate

“…This effect could have relevance to observations in both rodents and humans that exposure to specific odors can dramatically increase sensitivity to them [22][23][24][25][26][27] . Alternatively, or in addition, OSNs produced via odordependent neurogenesis could conceivably enable the formation of new OB glomeruli and connections with projection neurons [53][54][55][56] . Under this scenario, stimulation-dependent neurogenesis of specific subtypes could alter inputs to the olfactory cortex and thereby regulate the perception of, and behavioral responses to, specific odors.…”

Deficits in olfactory system neurogenesis in neurodevelopmental disorders

“…Sema‐neuropilin‐plexin signaling consists of secreted semaphorin ligands complexing with neuropilin co‐receptors and plexin receptors, and serves several functions relevant to OSNs: Sema 3F secreted by mitral, tufted, and periglomerular cells in the olfactory bulb (OB) is important for pruning of neuropilin‐2‐expressing OSN axons that overshoot into the external plexiform layer (EPL) (top left); repulsion occurs between non‐overlapping populations of OSN axons expressing Sema 3F and neuropilin‐2 (top right); Sema 3A secreted by mitral and tufted cells repels neuropilin‐1‐expressing OSN axons (bottom left); and repulsion between Sema 7A secreted by OSN axons and plexin C1 expressed by mitral and tufted cells is required for OSN synapse formation (bottom right) (Inoue et al, 2018). See Cho et al (2009), Dorrego‐Rivas and Grubb (2022), and Francia and Lodovichi (2021) for further details. Created with BioRender.com.…”

“…OSNs expressing the same receptor converge to form glomeruli, where they synapse with dendrites of excitatory and inhibitory OB neurons. However, odorant receptors collaborate with members of three of the most prominent families of axon guidance molecules: ephrin‐Ephs, Slit‐Robos, and semaphorin‐neuropilin‐plexins, to determine the position of individual glomeruli (Cho et al, 2009; Dorrego‐Rivas & Grubb, 2022; Francia & Lodovichi, 2021; Inoue et al, 2018) (Figure 2).…”