| First Author | Chatterjee S | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 7 | Pages | e68300 |
| PubMed ID | 23869214 | Mgi Jnum | J:204279 |
| Mgi Id | MGI:5532206 | Doi | 10.1371/journal.pone.0068300 |
| Citation | Chatterjee S, et al. (2013) The alpha5 subunit regulates the expression and function of alpha4*-containing neuronal nicotinic acetylcholine receptors in the ventral-tegmental area. PLoS One 8(7):e68300 |
| abstractText | Human genetic association studies have shown gene variants in the alpha5 subunit of the neuronal nicotinic receptor (nAChR) influence both ethanol and nicotine dependence. The alpha5 subunit is an accessory subunit that facilitates alpha4* nAChRs assembly in vitro. However, it is unknown whether this occurs in the brain, as there are few research tools to adequately address this question. As the alpha4*-containing nAChRs are highly expressed in the ventral tegmental area (VTA) we assessed the molecular, functional and pharmacological roles of alpha5 in alpha4*-containing nAChRs in the VTA. We utilized transgenic mice alpha5+/+(alpha4YFP) and alpha5-/-(alpha4YFP) that allow the direct visualization and measurement of alpha4-YFP expression and the effect of the presence (alpha5+/+) and absence of alpha5 (-/-) subunit, as the antibodies for detecting the alpha4* subunits of the nAChR are not specific. We performed voltage clamp electrophysiological experiments to study baseline nicotinic currents in VTA dopaminergic neurons. We show that in the presence of the alpha5 subunit, the overall expression of alpha4 subunit is increased significantly by 60% in the VTA. Furthermore, the alpha5 subunit strengthens baseline nAChR currents, suggesting the increased expression of alpha4* nAChRs to be likely on the cell surface. While the presence of the alpha5 subunit blunts the desensitization of nAChRs following nicotine exposure, it does not alter the amount of ethanol potentiation of VTA dopaminergic neurons. Our data demonstrates a major regulatory role for the alpha5 subunit in both the maintenance of alpha4*-containing nAChRs expression and in modulating nicotinic currents in VTA dopaminergic neurons. Additionally, the alpha5alpha4* nAChR in VTA dopaminergic neurons regulates the effect of nicotine but not ethanol on currents. Together, the data suggest that the alpha5 subunit is critical for controlling the expression and functional role of a population of alpha4*-containing nAChRs in the VTA. |
