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Olfactory receptor neuron

From Wikipedia, the free encyclopedia
(Redirected from Olfactory cells)
Olfactory receptor neuron
Olfactory mucosa (labels in German): Schleimschicht = mucus layer; Cilien = cilia; Riechsinneszellen = olfactory sensory neurons; Stützzellen = supporting cells; Basalzellen = basal cells; Bowman-Drüse = Bowman's gland; Riechnerv = olfactory nerve.
Details
SystemSmell
LocationOlfactory epithelium in the nose
ShapeBipolar sensory receptor
FunctionDetect traces of chemicals in inhaled air (sense of smell)
NeurotransmitterGlutamate[1]
Presynaptic connectionsNone
Postsynaptic connectionsOlfactory bulb
Identifiers
MeSHD018034
NeuroLex IDnifext_116
THH3.11.07.0.01003
FMA67860
Anatomical terms of neuroanatomy
Plan of olfactory neurons
Olfactory sensory neurons (OSNs) express odorant receptors. The axons of OSNs expressing the same odorant receptors converge onto corresponding glomerular targets in the olfactory bulb, allowing for the organization of olfactory information.

An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system.[2] ORNs are the principal neurons of the sense of smell: they detect volatile chemicals in inhaled air and convert that chemical signal into an electrical one that is relayed to the olfactory bulb of the brain.[2] Unusually for neurons, ORNs are continually replaced throughout life from stem cells in the olfactory epithelium.[3]

Molecular discovery

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A major advance in the molecular study of olfaction came in 1991, when Linda Buck and Richard Axel identified a large multigene family that they proposed encodes the odorant receptors, providing the first molecular handle on how ORNs detect odors.[4] Buck and Axel received the 2004 Nobel Prize in Physiology or Medicine for their discoveries concerning odorant receptors and the organization of the olfactory system.[5]

Structure

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Humans have between 10 and 20 million olfactory receptor neurons (ORNs).[6] In vertebrates, ORNs are bipolar neurons within the pseudostratified olfactory epithelium of the nasal cavity. Each mature neuron extends a short apical dendrite to the epithelial surface, where it ends in a knob bearing non-motile cilia within the mucus. A slender unmyelinated axon extends from the basal pole, joins the olfactory nerve and passes through the cribriform foramina of the cribriform plate before terminating in a glomerulus of the olfactory bulb.[3][7]

The olfactory epithelium contains sustentacular cells (supporting cells), which span the epithelium and support the ORNs, and basal cells near the basement membrane that act as progenitors. The olfactory glands (glands of Bowman) lie in the underlying lamina propria and secrete the mucus bathing the cilia through ducts that open onto the epithelial surface.[3][7]

Many tiny hair-like non-motile cilia protrude from the olfactory receptor cell's dendrites. The dendrites extend to the olfactory epithelial surface and each ends in a dendritic knob from which around 20 to 35 cilia protrude. The cilia have a length of up to 100 micrometers and with the cilia from other dendrites form a meshwork in the olfactory mucus.[7] The ORN dendrite integrates the receptor currents generated across these cilia.[8] The ciliary membrane contains olfactory receptors, a family of G protein-coupled receptors. Many separate olfactory receptor cells express ORs that bind the same set of odors, and the axons of mature canonical ORNs expressing the same receptor converge onto corresponding glomeruli in the olfactory bulb.[9]

Mature canonical ORNs generally express one allele of one OR gene.[10] Chromatin-mediated silencing, enhancer interactions and receptor-dependent feedback help establish and stabilize this singular receptor choice.[11] Because each OR recognizes multiple odorants and each odorant activates multiple ORs, the identity of an odor is encoded by the combination of receptors it activates.[12] The orderly convergence of same-receptor axons onto dedicated glomeruli preserves this receptor information as a spatial map in the olfactory bulb.[13]

Regeneration

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Unlike most neurons, ORNs are continuously replaced throughout life. New ORNs are generated from globose basal cells in the olfactory epithelium, while horizontal basal cells act as a reserve stem-cell pool that is recruited after injury.[3] Turnover is heterogeneous: some neurons are relatively short-lived, whereas mature neurons can persist for months, and the production of replacement neurons increases substantially after epithelial injury.[3] Odorant-receptor gene expression begins as newly generated ORNs differentiate and mature, as demonstrated during olfactory-neuron regeneration in the catfish and characterized during maturation in mice.[14][7] This lifelong neurogenesis is unusual among mammalian neurons and allows the olfactory epithelium to recover from environmental damage.[3]

Function

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In vertebrate ORNs, odorant receptors are G protein-coupled receptors located mainly in the membrane of the olfactory cilia.[15][2] There are approximately 1000 different genes that code for the ORs in the mouse, making them the largest gene family in the mammalian genome; humans have roughly 400 functional OR genes, the remainder having become pseudogenes.[16] An odorant dissolves into the mucus of the olfactory epithelium and binds to an OR. Individual ORs can respond to multiple odorants, and a single odorant can activate multiple ORs, producing a combinatorial receptor code.[12] Odorant binding activates the G protein Golf; its α-subunit, encoded by GNAL, stimulates adenylyl cyclase type III (ACIII) to produce cyclic AMP (cAMP). cAMP opens cyclic nucleotide-gated (CNG) channels, admitting Na+ and Ca2+. The rise in intracellular Ca2+ opens calcium-activated chloride channels, including TMEM16B/ANO2, and because olfactory neurons maintain a high internal chloride concentration, Cl− flows out of the cell, amplifying the depolarization and promoting action potential firing.[15]

The main olfactory epithelium also expresses smaller, distinct families of chemosensory receptors in subsets of neurons. Trace amine-associated receptors (TAARs) form a second class of receptors in the olfactory epithelium that detect volatile amines.[17] Distinct from the ORNs of the main olfactory epithelium, the vomeronasal organ (accessory olfactory system) of many vertebrates contains its own sensory neurons expressing unrelated families of putative pheromone receptors.[18]

Desensitization of olfactory neuron

Desensitization

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The olfactory receptor neuron has a fast working negative feedback response upon depolarization. When the neuron is depolarizing, the CNG ion channel is open allowing sodium and calcium to rush into the cell. Calcium entering through the CNG channels then promotes adaptation through several feedback pathways. Ca2+ binds to calmodulin, and the resulting Ca2+–calmodulin complex reduces the sensitivity of the CNG channel, limiting further sodium and calcium influx.[19] CaMKII, activated by Ca2+–calmodulin, can phosphorylate ACIII and reduce cAMP production,[20] while phosphodiesterases degrade cAMP.[21] Together these mechanisms reduce the neuron's responsiveness during sustained or repeated stimulation.

Number of distinguishable odors

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A widely publicized study suggested that humans can discriminate more than one trillion olfactory stimuli.[22] This finding has been disputed. Critics argued that the methodology used for the estimation was fundamentally flawed, showing that applying the same argument for better-understood sensory modalities, such as vision or audition, leads to wrong conclusions.[23] Other researchers argued that the formula used actually yields an upper bound rather than the lower bound reported, so the calculation supports "at most" one trillion, and is extremely sensitive to the precise details of the calculation, with small variations changing the result over tens of orders of magnitude, possibly going as low as a few thousand.[24] The authors of the original study have argued that their estimate holds as long as it is assumed that odor space is sufficiently high-dimensional.[25]

Other animals

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The number of functional olfactory receptor genes varies widely among species and contributes to differences in the range of chemicals their olfactory systems can represent. Mice have roughly 1,000 functional OR genes, whereas humans have only about 400, with many other mammals falling between these values.[16] Receptor-gene number alone, however, does not determine olfactory sensitivity or discrimination: despite their smaller receptor repertoire, humans can outperform rodents and dogs for particular odorants.[26]

Insects

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Insects also detect odors with olfactory receptor neurons, but their receptors are unrelated to the vertebrate GPCR family. Insect odorant receptors are heteromeric complexes of a variable odor-specific Or subunit and a conserved co-receptor (Orco), and they function mainly as ligand-gated ion channels.[27][28] A metabotropic, cyclic-nucleotide-activated component has also been reported, so the relative contribution of the two pathways is not fully settled.[29] The ionotropic signaling of these receptors is fast and direct.[30]

Dogs

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Compared to humans, dogs have a larger number of olfactory receptor neurons and a larger olfactory bulb, resulting in a remarkably sensitive sense of smell, which is used by law enforcement to detect dangerous and illegal substances and biological scents, as well as by agricultural and conservation scientists to detect other living organisms, such as plant parasites, endangered animals, invasive species and even microorganisms.[31]

Clinical significance

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Olfactory dysfunction, including reduced smell (hyposmia) and loss of smell (anosmia), is estimated to affect 3–20% of the population; risk increases with age and dysfunction can follow chronic sinonasal disease, head trauma, upper-respiratory infection or neurodegenerative disease.[32] Because ORNs are exposed directly to the inhaled environment, the olfactory epithelium is vulnerable to such damage and infection. In COVID-19, the viral-entry proteins ACE2 and TMPRSS2 are expressed mainly by non-neuronal sustentacular cells rather than by ORNs.[33][34] Infection of sustentacular cells can induce epithelial inflammation, damage olfactory cilia and reduce the expression of odorant receptors and olfactory signal-transduction proteins.[35][34] Persistent post-COVID-19 smell loss has been associated with continued immune-cell infiltration and altered gene expression in the olfactory epithelium,[36] and may also involve dysfunction of ORNs, the olfactory bulb and the olfactory cortex.[34]

See also

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References

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  1. ↑ Berkowicz, D. A.; Trombley, P. Q.; Shepherd, G. M. (1994). "Evidence for glutamate as the olfactory receptor cell neurotransmitter". Journal of Neurophysiology. 71 (6): 2557–61. doi:10.1152/jn.1994.71.6.2557. PMID 7931535.
  2. 1 2 3 Firestein S (September 2001). "How the olfactory system makes sense of scents". Nature. 413 (6852): 211–8. Bibcode:2001Natur.413..211F. doi:10.1038/35093026. PMID 11557990.
  3. 1 2 3 4 5 6 Schwob JE, Jang W, Holbrook EH, Lin B, Herrick DB, Peterson JN, et al. (March 2017). "Stem and progenitor cells of the mammalian olfactory epithelium: Taking poietic license". Journal of Comparative Neurology. 525 (4): 1034–1054. doi:10.1002/cne.24105. PMC 5805156. PMID 27560601.
  4. ↑ Buck L, Axel R (April 1991). "A novel multigene family may encode odorant receptors: a molecular basis for odor recognition". Cell. 65 (1): 175–87. Bibcode:1991Cell...65..175B. doi:10.1016/0092-8674(91)90418-x. PMID 1840504.
  5. ↑ Buck LB (September 2005). "Unraveling the sense of smell (Nobel lecture)". Angewandte Chemie (International ed. in English). 44 (38): 6128–40. doi:10.1002/anie.200501120. PMID 16175527.
  6. ↑ Saladin, Kenneth (2012). Anatomy & physiology : the unity of form and function (6th ed.). McGraw-Hill. p. 593. ISBN 978-0073378251.
  7. 1 2 3 4 McClintock, TS; Khan, N; Xie, C; Martens, JR (5 December 2020). "Maturation of the Olfactory Sensory Neuron and Its Cilia". Chemical Senses. 45 (9): 805–822. doi:10.1093/chemse/bjaa070. PMC 8133333. PMID 33075817.
  8. ↑ Vermeulen, A; Rospars, J. P. (1998). "Dendritic integration in olfactory sensory neurons: A steady-state analysis of how the neuron structure and neuron environment influence the coding of odor intensity". Journal of Computational Neuroscience. 5 (3): 243–66. doi:10.1023/A:1008826827728. PMID 9663551. S2CID 19598225.
  9. ↑ McEwen, D. P; Jenkins, Paul M; Martens, Jeffrey R (2008). "Olfactory cilia: our direct neuronal connection to the external world". Current Topics in Developmental Biology. 85: 333–370. doi:10.1016/S0070-2153(08)00812-0. ISBN 9780123744531. PMID 19147011.
  10. ↑ Chess A, Simon I, Cedar H, Axel R (September 1994). "Allelic inactivation regulates olfactory receptor gene expression". Cell. 78 (5): 823–34. doi:10.1016/s0092-8674(94)90562-2. PMID 8087849.
  11. ↑ Pourmorady A, Lomvardas S (February 2022). "Olfactory receptor choice: a case study for gene regulation in a multi-enhancer system". Current Opinion in Genetics & Development. 72: 101–9. doi:10.1016/j.gde.2021.11.003. PMC 12734978. PMID 34896807.
  12. 1 2 Malnic B, Hirono J, Sato T, Buck LB (March 1999). "Combinatorial receptor codes for odors". Cell. 96 (5): 713–23. Bibcode:1999Cell...96..713M. doi:10.1016/s0092-8674(00)80581-4. PMID 10089886.
  13. ↑ Mori K, Sakano H (2011). "How is the olfactory map formed and interpreted in the mammalian brain?". Annual Review of Neuroscience. 34: 467–99. doi:10.1146/annurev-neuro-112210-112917. PMID 21469960.
  14. ↑ Fan, Jinhong; Ngai, John (2001). "Onset of Odorant Receptor Gene Expression during Olfactory Sensory Neuron Regeneration". Developmental Biology. 229 (1): 119–27. doi:10.1006/dbio.2000.9972. PMID 11133158.
  15. 1 2 Kaupp UB (March 2010). "Olfactory signalling in vertebrates and insects: differences and commonalities". Nature Reviews Neuroscience. 11 (3): 188–200. doi:10.1038/nrn2789. PMID 20145624.
  16. 1 2 Niimura Y (April 2012). "Olfactory receptor multigene family in vertebrates: from the viewpoint of evolutionary genomics". Current Genomics. 13 (2): 103–14. doi:10.2174/138920212799860706. PMC 3308321. PMID 23024602.
  17. ↑ Liberles SD, Buck LB (August 2006). "A second class of chemosensory receptors in the olfactory epithelium". Nature. 442 (7103): 645–50. Bibcode:2006Natur.442..645L. doi:10.1038/nature05066. PMID 16878137.
  18. ↑ Dulac C, Axel R (October 1995). "A novel family of genes encoding putative pheromone receptors in mammals". Cell. 83 (2): 195–206. Bibcode:1995Cell...83..195D. doi:10.1016/0092-8674(95)90161-2. PMID 7585937.
  19. ↑ Bradley, J; Reuter, D; Frings, S (2001). "Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits". Science. 294 (5549): 2176–2178. Bibcode:2001Sci...294.2176B. doi:10.1126/science.1063415. PMID 11739960. S2CID 13357941.
  20. ↑ Wei, J; Zhao, AZ; Chan, GC; Baker, LP; Impey, S; Beavo, JA; Storm, DR (1998). "Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in Neurons: a mechanism for attenuation of olfactory signals". Neuron. 21 (3): 495–504. doi:10.1016/s0896-6273(00)80561-9. PMID 9768837. S2CID 9860137.
  21. ↑ Yan, C; Zhao, AZ; Bentley, JK; Loughney, K; Ferguson, K; Beavo, JA (1995). "Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons". Proceedings of the National Academy of Sciences. 92 (21): 9677–9681. Bibcode:1995PNAS...92.9677Y. doi:10.1073/pnas.92.21.9677. PMC 40865. PMID 7568196.
  22. ↑ Bushdid, C.; Magnasco, M. O.; Vosshall, L. B.; Keller, A. (2014). "Humans Can Discriminate More than 1 Trillion Olfactory Stimuli". Science. 343 (6177): 1370–2. Bibcode:2014Sci...343.1370B. doi:10.1126/science.1249168. PMC 4483192. PMID 24653035.
  23. ↑ Meister, Markus (2015). "On the dimensionality of odor space". eLife. 4 e07865. doi:10.7554/eLife.07865. PMC 4491593. PMID 26151672.
  24. ↑ Gerkin, Richard C.; Castro, Jason B. (2015). "The number of olfactory stimuli that humans can discriminate is still unknown". eLife. 4 e08127. doi:10.7554/eLife.08127. PMC 4491703. PMID 26151673.
  25. ↑ Magnasco, Marcelo O.; Keller, Andreas; Vosshall, Leslie B. (2015). "On the dimensionality of olfactory space". bioRxiv 10.1101/022103.
  26. ↑ McGann JP (May 2017). "Poor human olfaction is a 19th-century myth". Science. 356 (6338) eaam7263. doi:10.1126/science.aam7263. PMC 5512720. PMID 28495701.
  27. ↑ Sato K, Pellegrino M, Nakagawa T, Nakagawa T, Vosshall LB, Touhara K (April 2008). "Insect olfactory receptors are heteromeric ligand-gated ion channels". Nature. 452 (7190): 1002–6. Bibcode:2008Natur.452.1002S. doi:10.1038/nature06850. PMID 18408712.
  28. ↑ Touhara, Kazushige (2009). "Insect Olfactory Receptor Complex Functions as a Ligand-gated Ionotropic Channel". Annals of the New York Academy of Sciences. 1170 (1): 177–80. Bibcode:2009NYASA1170..177T. doi:10.1111/j.1749-6632.2009.03935.x. PMID 19686133. S2CID 6336906.
  29. ↑ Wicher D, Schäfer R, Bauernfeind R, Stensmyr MC, Heller R, Heinemann SH, et al. (April 2008). "Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels". Nature. 452 (7190): 1007–11. Bibcode:2008Natur.452.1007W. doi:10.1038/nature06861. PMID 18408711.
  30. ↑ Su CY, Menuz K, Carlson JR (October 2009). "Olfactory perception: receptors, cells, and circuits". Cell. 139 (1): 45–59. doi:10.1016/j.cell.2009.09.015. PMC 2765334. PMID 19804753.
  31. ↑ Kokocińska-Kusiak, Agata; Woszczyło, Martyna; Zybala, Mikołaj; Maciocha, Julia; Barłowska, Katarzyna; Dzięcioł, Michał (21 August 2021). "Canine Olfaction: Physiology, Behavior, and Possibilities for Practical Applications". Animals. 11 (8) 2463. doi:10.3390/ani11082463. PMC 8388720. PMID 34438920.
  32. ↑ Boesveldt S, Postma EM, Boak D, Welge-Luessen A, Schöpf V, Mainland JD, et al. (September 2017). "Anosmia-A Clinical Review". Chemical Senses. 42 (7): 513–23. doi:10.1093/chemse/bjx025. PMC 5863566. PMID 28531300.
  33. ↑ Brann DH, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, et al. (July 2020). "Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia". Science Advances. 6 (31) eabc5801. doi:10.1126/sciadv.abc5801. PMC 10715684. PMID 32937591.
  34. 1 2 3 Chang K, Zaikos TD, Kilner-Pontone N, Ho CY (April 2024). "Mechanisms of COVID-19-associated olfactory dysfunction". Neuropathology and Applied Neurobiology. 50 (2) e12960. doi:10.1111/nan.12960. PMC 10906737. PMID 38419211.
  35. ↑ Verma AK, Zheng J, Meyerholz DK, Perlman S (December 2022). "SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways". JCI Insight. 7 (24) e160277. doi:10.1172/jci.insight.160277. PMC 9869979. PMID 36378534.
  36. ↑ Finlay JB, Brann DH, Abi Hachem R, Jang DW, Oliva AD, Ko T, et al. (December 2022). "Persistent post-COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium". Science Translational Medicine. 14 (676) eadd0484. doi:10.1126/scitranslmed.add0484. PMC 10317309. PMID 36542694.
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