α6* Nicotinic Acetylcholine Receptor Expression and Function in a Visual Salience Circuit

• DOI: 10.1523/jneurosci.0007-12.2012
• Publication Date: 2012-08-01T18:06:15Z
• Authors: Elisha D.W. Mackey; Staci E. Engle; Mi Ran Kim; Heidi C. O'Neill; Charles R. Wageman; Natalie E. Patzlaff; Ying Wang; Sharon R. Grady; J. Michael McIntosh; Michael J. Marks; Henry A. Lester; Ryan M. Drenan
• Keywords: Neurons; Superior Colliculi; 0303 health sciences; Dopamine; 610; Mice, Transgenic; Receptors, Nicotinic; Mice; 03 medical and health sciences; 616; Synapses; Animals; Visual Pathways; GABAergic Neurons; gamma-Aminobutyric Acid

Nicotinic acetylcholine receptors (nAChRs) containing α6 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 α6-containing nAChRs, we created and studied transgenic mice expressing a variant α6 subunit with green fluorescent protein (GFP) fused in-frame in the M3-M4 intracellular loop. In α6-GFP transgenic mice, α6-dependent synaptosomal DA release and radioligand binding experiments confirmed correct expression and function in vivo . In addition to strong α6* nAChR expression in glutamatergic retinal axons, which terminate in superficial superior colliculus (sSC), we also found α6 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 α6* nAChRs, we confirmed functional, postsynaptic α6* nAChR expression. Further, sSC GABAergic neurons expressing α6* nAChRs exhibit a tonic conductance mediated by standing activation of hypersensitive α6* nAChRs by ACh. α6* nAChRs also appear in a subpopulation of SC neurons in output layers. Finally, selective activation of α6* nAChRs in vivo induced sSC neuronal activation as measured with c-Fos expression. Together, these results demonstrate that α6* 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 α6* nAChRs may be important for nicotinic cholinergic sensitization of this pathway.