Odors Detected by Mice Deficient in Cyclic Nucleotide-Gated Channel Subunit A2 Stimulate the Main Olfactory System

Lin, Weihong; Arellano, Julie; Slotnick, Burton M.; Restrepo, Diego

doi:10.1523/jneurosci.0188-04.2004

Cited by 126 publications

(124 citation statements)

References 37 publications

(62 reference statements)

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“…In addition, MOE responses to MHC peptides are inhibited by adenylcyclase antagonists and critically depend on a functional CNGA4 gene, which encodes a principal subunit of a cyclic AMP-sensitive CNG channel expressed in MOE but not in the VNO, thus showing that MHC peptides ligands are transduced in the MOE by cells employing a cAMP-signaling pathway and the olfactory CNG channel. Similar results have been obtained with the odorant 2-heptanone: its detection appears to be dependent on the Trp2 gene in the VNO, while in the MOE, detection of 2-heptanone depends on the CNGA2 [60,63]. At the behavioral level, this processing of the same olfactory signals is not just a redundancy.…”

Section: Functional Roles Of Both the Main And The Accessory Olfactorsupporting

confidence: 79%

“…Such AC3 KO mice were able to detect several volatile odorants, including putative pheromones, presumably via the VNO. However, more recently it was shown that mice defective in the olfactory cAMP signaling pathway can detect some volatile odorants through their olfactory epithelium using alternative transduction pathways [63].…”

Section: Functional Roles Of Both the Main And The Accessory Olfactormentioning

confidence: 99%

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The main and the accessory olfactory systems interact in the control of mate recognition and sexual behavior

Keller

Baum

Brock

et al. 2009

Behavioural Brain Research

150

101

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Section: Functional Roles Of Both the Main And The Accessory Olfactorsupporting

confidence: 79%

Section: Functional Roles Of Both the Main And The Accessory Olfactormentioning

confidence: 99%

The main and the accessory olfactory systems interact in the control of mate recognition and sexual behavior

Keller

Baum

Brock

et al. 2009

Behavioural Brain Research

150

101

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“…By contrast to Ano2 -/-mice, Cnga2 -/y mice 31 showed a clear-cut impairment in the same test (Fig. 8a), as reported 25,30 . Discrimination ability was neither reduced in more complex discrimination tasks such as distinguishing hexanal from octanal ( Fig.…”

Section: No Olfactory Deficits Detected In Ano2 -/-Micesupporting

confidence: 79%

“…4e) showed no change in the amount of tyrosine hydroxylase in the olfactory bulb, either. The expression of this enzyme depends on neuronal activity and was severely reduced in the olfactory bulb of anosmic Cnga2 -/y mice 30 . OSN axon coalescence on glomeruli is perturbed in mice lacking functional CNG channels 31 or the adenylate cyclase 32 .…”

Section: No Change Of Key Proteins and Axonal Convergencementioning

confidence: 98%

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Ca2+-activated Cl− currents are dispensable for olfaction

et al. 2011

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Graduate student at the Freie Universität Berlin Olfaction in mammals involves the binding of odorants to a subset of the large number of different G protein-coupled receptors that are present in the cilia of olfactory sensory neurons (OSNs) 1 . These neurons are predominantly found in the MOE, which senses and discriminates myriad volatile compounds. In the mouse, the nose contains additional, apparently more specialized olfactory organs, such the septal organ of Masera and the VNO 2 . Sensory neurons in the VNO are morphologically distinct and use odorant receptors and signal transduction cascades that differ from those found in the MOE.In the canonical OSN signal transduction pathway, odorant binding to the receptor locally increases cytosolic cAMP through activation of the olfactory G protein G olf and adenylate cyclase type III 1,2 . cAMP then opens heteromeric cyclic nucleotide-gated (CNG) cation channels 3 . The resulting influx of Na + and Ca 2+ depolarizes the plasma membrane and raises the cytosolic Ca 2+ concentration ([Ca 2+ ] i ), thereby activating Ca 2+ -activated Cl -channels 1,4-10 . All these components of the signal transduction cascade are localized to sensory cilia, which are embedded in the mucus covering the MOE. These cilia provide a large interaction surface for odorants, and the cilia's small diameters facilitate large local increases in cytosolic cAMP and [Ca 2+ ].There has been broad consensus that Ca 2+ -activated Cl -channels powerfully amplify olfactory signal transduction 1,4-10 . These channels are thought to mediate an outward flow of Cl -, which generates a depolarizing current that, in rodents, is five-to tenfold larger than currents through CNG channels 8,11,12 . A prerequisite for Cl -efflux 3 is an inside-out electrochemical Cl --gradient. It is believed that cytosolic chloride concentration of OSNs is raised by the Na + K + 2Cl -co-transporter Nkcc1 9,10,13 and that [Cl -] is low in the mucus surrounding the cilia 14,15 . However, mucosal ion concentrations are difficult to measure in vivo, and Nkcc1 knockout mice display attenuated electro-olfactograms (EOGs) 11,16 , but normal olfactory sensitivity 17 .To investigate the role of Ca 2+ -activated Cl -channels in olfaction, we disrupted Ano2 in mice. Ano2 is a member of the Anoctamin (Tmem16) gene family, which encodes several Ca 2+ -activated Cl -channels [18][19][20] . Agreeing with recent results 13,21-23 , our knockout-controlled immunolabeling showed Ano2 expression in cilia of OSNs in the MOE, in microvilli of VNO sensory neurons and in synapses of photoreceptors. Additionally, we found Ano2 in the olfactory bulb. Ano1 expression overlapped with Ano2 in the VNO and the retina, but not in the MOE. Patch-clamp analysis showed that Ca 2+ -activated Cl -currents were undetectable in Ano2 -/-OSNs.Unexpectedly, however, EOGs of Ano2 -/-mice were reduced by only up to ~40%, and Ano2 -/-mice were able to smell normally. Our work calls for a revision of the current view that Ca 2+ -activated Cl -channels have a crucial role...

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Olfactometry with Mice

Slotnick

Restrepo

2005

CP Neuroscience

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A computer-controlled, multiple-channel odor generator, operant test chamber, and discrimination training procedure for mice are described. The odor generator allows controlled presentation of any one or combinations of eight odors to an odor-sampling port that contains a liquid reinforcement delivery tube that also serves to detect responses. A modified discrete trial operant conditioning procedure provides measures of both response accuracy and response rate during anticipation of stimulus delivery and in the presence of two different odor stimuli. Results from numerous experiments demonstrate that, with these methods, mice reliably and rapidly acquire odor detection and a variety of odor-discrimination tasks, and that response rate in the presence of the odor reflects the incentive motivation of stimuli that are or are not associated with reward.

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Odors Detected by Mice Deficient in Cyclic Nucleotide-Gated Channel Subunit A2 Stimulate the Main Olfactory System

Cited by 126 publications

References 37 publications

The main and the accessory olfactory systems interact in the control of mate recognition and sexual behavior

The main and the accessory olfactory systems interact in the control of mate recognition and sexual behavior

Ca2+-activated Cl− currents are dispensable for olfaction

Olfactometry with Mice

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