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| Research article summary (published 16 Feb 2009): |
Rodent habenulo-interpeduncular pathway expresses a large variety of uncommon nAChR subtypes, but only the alpha3beta4* and alpha3beta3beta4* subtypes mediate acetylcholine release.
Full Abstract
Recent studies suggest that the neuronal nicotinic receptors (nAChRs) present in the habenulo-interpeduncular (Hb-IPn) system can modulate the reinforcing effect of addictive drugs and the anxiolytic effect of nicotine. Hb and IPn neurons express mRNAs for most nAChR subunits, thus making it difficult to establish the subunit composition of functional receptors. We used immunoprecipitation and immunopurification studies performed in rat and wild-type (+/+) and beta2 knock-out (-/-) mice to establish that the Hb and IPn contain significant beta2* and beta4* populations of nAChR receptors (each of which is heterogeneous). The beta4* nAChR are more highly expressed in the IPn. We also identified novel native subtypes (alpha2beta2*, alpha4beta3beta2*, alpha3beta3beta4*, alpha6beta3beta4*). Our studies on IPn synaptosomes obtained from +/+ and alpha2, alpha4, alpha5, alpha6, alpha7, beta2, beta3, and beta4(-/-) mice show that only the alpha3beta4 and alpha3beta3beta4 subtypes facilitate acetylcholine (ACh) release. Ligand binding, immunoprecipitation, and Western blotting studies in beta3(-/-) mice showed that, in the IPn of these mice, there is a concomitant reduction of ACh release and alpha3beta4* receptors, whereas the receptor number remains the same in the Hb. We suggest that, in habenular cholinergic neurons, the beta3 subunit may be important for transporting the alpha3beta4* subtype from the medial habenula to the IPn. Overall, these studies highlight the presence of a wealth of uncommon nAChR subtypes in the Hb-IPn system and identify alpha3beta4 and alpha3beta3beta4, transported from the Hb and highly enriched in the IPn, as the subtypes modulating ACh release in the IPn.
Author information
Author/s: Grady, Sharon R (SR); Moretti, Milena (M); Zoli, Michele (M); Marks, Michael J (MJ); Zanardi, Alessio (A); Pucci, Luca (L); Clementi, Francesco (F); Gotti, Cecilia (C);
Affiliation: Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado 80301, USA.
Grants: DA003194 (Agency:NIDA NIH HHS) ; DA015663 (Agency:NIDA NIH HHS) ; P30 DA015663-04 (Agency:NIDA NIH HHS) ; P30 DA015663-05 (Agency:NIDA NIH HHS) ; P30 DA015663-05S1 (Agency:NIDA NIH HHS) ; R01 DA003194-24 (Agency:NIDA NIH HHS) ; R01 DA003194-25 (Agency:NIDA NIH HHS) ; R01 DA003194-26 (Agency:NIDA NIH HHS)
Journal and publication information
Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)
Reference: 2009-Feb; vol 29 (issue 7) : pp 2272-82
Dates: Created 2009/02/20; Completed 2009/04/16; Revised 2009/08/19;
PMID: 19228980, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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