Editing Olfactory receptor neuron (section)

==Function==
ORs, which are located on the membranes of the cilia have been classified as a complex type of [[ligand-gated]] metabotropic channels.<ref>{{cite journal |doi=10.1111/j.1749-6632.2009.03935.x |pmid=19686133 |title=Insect Olfactory Receptor Complex Functions as a Ligand-gated Ionotropic Channel |journal=Annals of the New York Academy of Sciences |volume=1170 |issue=1 |pages=177–80 |year=2009 |last1=Touhara |first1=Kazushige |bibcode=2009NYASA1170..177T |s2cid=6336906 }}</ref>  There are approximately 1000 different genes that code for the ORs, making them the largest gene family.  An [[odorant]] will dissolve into the mucus of the olfactory epithelium and then bind to an OR.  ORs can bind to a variety of odor molecules, with varying affinities.  The difference in affinities causes differences in activation patterns resulting in unique odorant profiles.<ref>{{cite journal |doi=10.1093/chemse/bjh050 |pmid=15269120 |title=Olfactory Receptor Neuron Profiling using Sandalwood Odorants |journal=Chemical Senses |volume=29 |issue=6 |pages=483–7 |year=2004 |last1=Bieri |first1=S. |last2=Monastyrskaia |first2=K |last3=Schilling |first3=B |doi-access=free }}</ref><ref>{{cite journal |doi=10.1006/dbio.2000.9972 |pmid=11133158 |title=Onset of Odorant Receptor Gene Expression during Olfactory Sensory Neuron Regeneration |journal=Developmental Biology |volume=229 |issue=1 |pages=119–27 |year=2001 |last1=Fan |first1=Jinhong |last2=Ngai |first2=John |doi-access=free }}</ref> The activated OR in turn activates the intracellular G-protein, GOLF ([[GNAL]]), [[adenylate cyclase]] and production of [[cyclic AMP]] (cAMP) opens [[ion channels]] in the [[cell membrane]], resulting in an influx of [[sodium]] and [[calcium]] ions into the cell, and an efflux of [[chloride]] ions. This influx of positive ions and efflux of negative ions causes the neuron to depolarize, generating an [[action potential]].

[[File:Desensitization of olfactory neuron.jpg|thumb|Desensitization of olfactory neuron]]

===Desensitization===
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. The influx of calcium begins a cascade of events within the cell. Calcium first binds to calmodulin to form [[CaM]]. CaM will then bind to the CNG channel and close it, stopping the sodium and calcium influx.<ref>{{cite journal | last1 = Bradley | first1 = J | last2 = Reuter | first2 = D | last3 = Frings | first3 = S | year = 2001 | title = Facilitation of calmodulinmediated odor adaptation by cAMP-gated channel subunits | journal = Science | volume = 294 | issue = 5549| pages = 2176–2178 | doi=10.1126/science.1063415 | pmid=11739960| bibcode = 2001Sci...294.2176B | s2cid = 13357941 }}</ref> [[CaMKII]] will be activated by the presence of CaM, which will phosphorylate ACIII and reduce cAMP production.<ref>{{cite journal | last1 = Wei | first1 = J | last2 = Zhao | first2 = AZ | last3 = Chan | first3 = GC | last4 = Baker | first4 = LP | last5 = Impey | first5 = S | last6 = Beavo | first6 = JA | last7 = Storm | first7 = DR | year = 1998 | title = Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in Neurons: a mechanism for attenuation of olfactory signals | journal = Neuron | volume = 21 | issue = 3| pages = 495–504 | doi=10.1016/s0896-6273(00)80561-9 | pmid=9768837| s2cid = 9860137 | doi-access = free }}</ref> CaMKII will also activate [[phosphodiesterase]], which will then hydrolyze cAMP.<ref>{{cite journal | last1 = Yan | first1 = C | last2 = Zhao | first2 = AZ | last3 = Bentley | first3 = JK | last4 = Loughney | first4 = K | last5 = Ferguson | first5 = K | last6 = Beavo | first6 = JA | year = 1995 | title = Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons | journal = Proc Natl Acad Sci USA | volume = 92 | issue = 21| pages = 9677–9681 | doi=10.1073/pnas.92.21.9677| pmid = 7568196 | pmc = 40865 | bibcode = 1995PNAS...92.9677Y | doi-access = free }}</ref> The effect of this negative feedback response inhibits the neuron from further activation when another odor molecule is introduced.

===Number of distinguishable odors===
A widely publicized study suggested that humans can detect more than one trillion different odors.<ref>{{cite journal |doi=10.1126/science.1249168 |pmid=24653035 |title=Humans Can Discriminate More than 1 Trillion Olfactory Stimuli |journal=Science |volume=343 |issue=6177 |year=2014 |last1=Bushdid |first1=C. |last2=Magnasco |first2=M. O. |last3=Vosshall |first3=L. B. |last4=Keller |first4=A. |bibcode=2014Sci...343.1370B |pages=1370–2 |pmc=4483192}}</ref> 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.<ref>{{cite journal|doi=10.7554/eLife.07865|pmid=26151672|pmc=4491593|title=On the dimensionality of odor space|last1=Meister|first1=Markus|volume=4|pages=e07865|journal=eLife|year=2015 |doi-access=free }}</ref> Other researchers have also showed that the result is extremely sensitive to the precise details of the calculation, with small variations changing the result over dozens of orders of magnitude, possibly going as low as a few thousand.<ref>{{cite journal|doi=10.7554/eLife.08127|pmid=26151673|pmc=4491703|title=The number of olfactory stimuli that humans can discriminate is still unknown|first1=Richard C.|last1=Gerkin|first2=Jason B.|last2=Castro|volume=4|pages=e08127|journal=eLife|year=2015 |doi-access=free }}</ref> 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.<ref>{{cite journal |doi=10.1101/022103|title=On the dimensionality of olfactory space|year=2015|last1=Magnasco|first1=Marcelo O.|last2=Keller|first2=Andreas|last3=Vosshall|first3=Leslie B.|doi-access=free}}</ref>