| First Author | Parker RL | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 12 | Pages | e0188715 |
| PubMed ID | 29206881 | Mgi Jnum | J:254937 |
| Mgi Id | MGI:6103724 | Doi | 10.1371/journal.pone.0188715 |
| Citation | Parker RL, et al. (2017) Deletion of lynx1 reduces the function of alpha6* nicotinic receptors. PLoS One 12(12):e0188715 |
| abstractText | The alpha6 nicotinic acetylcholine receptor (nAChR) subunit is an attractive drug target for treating nicotine addiction because it is present at limited sites in the brain including the reward pathway. Lynx1 modulates several nAChR subtypes; lynx1-nAChR interaction sites could possibly provide drug targets. We found that dopaminergic cells from the substantia nigra pars compacta (SNc) express lynx1 mRNA transcripts and, as assessed by co-immunoprecipitation, alpha6 receptors form stable complexes with lynx1 protein, although co-transfection with lynx1 did not affect nicotine-induced currents from cell lines transfected with alpha6 and beta2. To test whether lynx1 is important for the function of alpha6 nAChRs in vivo, we bred transgenic mice carrying a hypersensitive mutation in the alpha6 nAChR subunit (alpha6L9''S) with lynx1 knockout mice, providing a selective probe of the effects of lynx1 on alpha6* nAChRs. Lynx1 removal reduced the alpha6 component of nicotine-mediated rubidium efflux and dopamine (DA) release from synaptosomal preparations with no effect on numbers of alpha6beta2 binding sites, indicating that lynx1 is functionally important for alpha6* nAChR activity. No effects of lynx1 removal were detected on nicotine-induced currents in slices from SNc, suggesting that lynx1 affects presynaptic alpha6* nAChR function more than somatic function. In the absence of agonist, lynx1 removal did not alter DA release in dorsal striatum as measured by fast scan cyclic voltammetry. Lynx1 removal affected some behaviors, including a novel-environment assay and nicotine-stimulated locomotion. Trends in 24-hour home-cage behavior were also suggestive of an effect of lynx1 removal. Conditioned place preference for nicotine was not affected by lynx1 removal. The results show that some functional and behavioral aspects of alpha6-nAChRs are modulated by lynx1. |
