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Demonstration of functional α4-containing nicotinic receptors in the medial habenula

Fonck, Carlos and Nashmi, Raad and Salas, Ramiro and Zhou, Chunyi and Huang, Qi and De Biasi, Mariella and Lester, Robin A. J. and Lester, Henry A. (2008) Demonstration of functional α4-containing nicotinic receptors in the medial habenula. Neuropharmacology, 56 (1). pp. 247-253. ISSN 0028-3908. http://resolver.caltech.edu/CaltechAUTHORS:FONnp09

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Abstract

The medial habenula (MHb) exhibits exceptionally high levels of nicotinic acetylcholine receptors (nAChRs), but it remains unclear whether all expressed nAChR subunit mRNAs are translated to form functional receptors. In particular α4 subunits have not been reported to have any functional role, despite strong α4 mRNA expression in the ventrolateral MHb. We studied a strain of knock-in mice expressing fluorescent α4* nAChRs (α4YFP), as well as a knock-in strain expressing hypersensitive α4* nAChRs (α4L9'A). In α4YFP mice, there was strong fluorescence in the ventrolateral MHb. In hypersensitive α4L9'A mice, injections of a low dose of nicotine (0.1 mg/kg) led to strong c-fos expression in only the ventrolateral region of the MHb, but not in the MHb of wild-type (WT) mice. In MHb slice recordings, ventrolateral neurons from α4L9'A mice, but not from WT mice, responded robustly to nicotine (1 μM). Neurons in the medial aspect of the MHb had >10-fold smaller responses. Thus α4* nAChRs contribute to the selective activation of a subset of MHb neurons. Subunit composition analysis based on gain-offunction knock-in mice provides a useful experimental paradigm.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.neuropharm.2008.08.021DOIUNSPECIFIED
Additional Information:© 2008 Elsevier Ltd. Received 6 August 2008; accepted 8 August 2008; available online 26 August 2008. This work was supported by PHS grants NS31669, DA17173, DA17279, California Tobacco-Related Disease Research Project, and the Philip Morris External Research Fund. R.N. was supported by a NARSAD Young Investigator Award.
Funders:
Funding AgencyGrant Number
PHSNS31669
PHSDA17173
PHSDA17279
California Tobacco-Related Disease Research ProjectUNSPECIFIED
Philip Morris External Research FundUNSPECIFIED
NARSAD Young Investigator AwardUNSPECIFIED
Subject Keywords:Addiction; Ion channel; C-fos; Knock-in; mRNA
Record Number:CaltechAUTHORS:FONnp09
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:FONnp09
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13433
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:22 Apr 2009 18:23
Last Modified:26 Dec 2012 10:50

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