| First Author | Mackey ED | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 30 | Pages | 10226-37 |
| PubMed ID | 22836257 | Mgi Jnum | J:304873 |
| Mgi Id | MGI:6512102 | Doi | 10.1523/JNEUROSCI.0007-12.2012 |
| Citation | Mackey ED, et al. (2012) alpha6* nicotinic acetylcholine receptor expression and function in a visual salience circuit. J Neurosci 32(30):10226-37 |
| abstractText | Nicotinic acetylcholine receptors (nAChRs) containing alpha6 subunits are expressed in only a few brain areas, including midbrain dopamine (DA) neurons, noradrenergic neurons of the locus ceruleus, and retinal ganglion cells. To better understand the regional and subcellular expression pattern of alpha6-containing nAChRs, we created and studied transgenic mice expressing a variant alpha6 subunit with green fluorescent protein (GFP) fused in-frame in the M3-M4 intracellular loop. In alpha6-GFP transgenic mice, alpha6-dependent synaptosomal DA release and radioligand binding experiments confirmed correct expression and function in vivo. In addition to strong alpha6* nAChR expression in glutamatergic retinal axons, which terminate in superficial superior colliculus (sSC), we also found alpha6 subunit expression in a subset of GABAergic cell bodies in this brain area. In patch-clamp recordings from sSC neurons in brain slices from mice expressing hypersensitive alpha6* nAChRs, we confirmed functional, postsynaptic alpha6* nAChR expression. Further, sSC GABAergic neurons expressing alpha6* nAChRs exhibit a tonic conductance mediated by standing activation of hypersensitive alpha6* nAChRs by ACh. alpha6* nAChRs also appear in a subpopulation of SC neurons in output layers. Finally, selective activation of alpha6* nAChRs in vivo induced sSC neuronal activation as measured with c-Fos expression. Together, these results demonstrate that alpha6* nAChRs are uniquely situated to mediate cholinergic modulation of glutamate and GABA release in SC. The SC has emerged as a potential key brain area responsible for transmitting short-latency salience signals to thalamus and midbrain DA neurons, and these results suggest that alpha6* nAChRs may be important for nicotinic cholinergic sensitization of this pathway. |
