Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance

<p>Abstract</p> <p>Background</p> <p>The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a s...

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Main Authors: Knott Thomas K, Madany Pasil A, Faden Ashley A, Xu Mei, Strotmann Jörg, Henion Timothy R, Schwarting Gerald A
Format: Article
Language:English
Published: BMC 2012-07-01
Series:Neural Development
Subjects:
Online Access:http://www.neuraldevelopment.com/content/7/4/17
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author Knott Thomas K
Madany Pasil A
Faden Ashley A
Xu Mei
Strotmann Jörg
Henion Timothy R
Schwarting Gerald A
author_facet Knott Thomas K
Madany Pasil A
Faden Ashley A
Xu Mei
Strotmann Jörg
Henion Timothy R
Schwarting Gerald A
author_sort Knott Thomas K
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2<sup>−/−</sup> mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2<sup>−/−</sup> neurons.</p> <p>Results</p> <p>Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2<sup>−/−</sup> mice compared to controls. Analysis of OR expression by quantitative PCR and <it>in situ</it> hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2<sup>−/−</sup> olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2<sup>−/−</sup> mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, <it>in situ</it> hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2<sup>−/−</sup> olfactory neurons.</p> <p>Conclusions</p> <p>Results presented here show that many odorant receptors are under-expressed in β3GnT2<sup>−/−</sup> mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2<sup>−/−</sup> mice exhibit a relatively small deficit in their ability to discriminate divergent odors. Results suggest that despite the fact that β3GnT2<sup>−/−</sup> mice have decreased AC3 activity, decreased expression of many ORs, and display many axon growth and guidance errors, odor-evoked activity in cilia of mutant olfactory neurons remains largely intact.</p>
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spelling doaj.art-e3a77db08aa844e1bad717c1a51f42622022-12-22T02:45:06ZengBMCNeural Development1749-81042012-07-01711710.1186/1749-8104-7-17Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidanceKnott Thomas KMadany Pasil AFaden Ashley AXu MeiStrotmann JörgHenion Timothy RSchwarting Gerald A<p>Abstract</p> <p>Background</p> <p>The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that β3GnT2<sup>−/−</sup> mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in β3GnT2<sup>−/−</sup> neurons.</p> <p>Results</p> <p>Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in β3GnT2<sup>−/−</sup> mice compared to controls. Analysis of OR expression by quantitative PCR and <it>in situ</it> hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in β3GnT2<sup>−/−</sup> olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in β3GnT2<sup>−/−</sup> mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, <it>in situ</it> hybridization studies indicate that the expression of several activity dependent genes is unaffected in β3GnT2<sup>−/−</sup> olfactory neurons.</p> <p>Conclusions</p> <p>Results presented here show that many odorant receptors are under-expressed in β3GnT2<sup>−/−</sup> mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and β3GnT2<sup>−/−</sup> mice exhibit a relatively small deficit in their ability to discriminate divergent odors. Results suggest that despite the fact that β3GnT2<sup>−/−</sup> mice have decreased AC3 activity, decreased expression of many ORs, and display many axon growth and guidance errors, odor-evoked activity in cilia of mutant olfactory neurons remains largely intact.</p>http://www.neuraldevelopment.com/content/7/4/17Olfactory sensory neuronsβ3GnT2Adenylyl cyclase 3Axonal convergence
spellingShingle Knott Thomas K
Madany Pasil A
Faden Ashley A
Xu Mei
Strotmann Jörg
Henion Timothy R
Schwarting Gerald A
Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance
Neural Development
Olfactory sensory neurons
β3GnT2
Adenylyl cyclase 3
Axonal convergence
title Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance
title_full Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance
title_fullStr Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance
title_full_unstemmed Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance
title_short Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance
title_sort olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance
topic Olfactory sensory neurons
β3GnT2
Adenylyl cyclase 3
Axonal convergence
url http://www.neuraldevelopment.com/content/7/4/17
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