title: α6* nicotinic acetylcholine receptor expression and function in a visual salience circuit.
abstract: 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.
authors: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
authors: Elisha D W
authors: ED
authors: Mackey
authors: Staci E
authors: SE
authors: Engle
authors: Mi Ran
authors: MR
authors: Kim
authors: Heidi C
authors: HC
authors: O'Neill
authors: Charles R
authors: CR
authors: Wageman
authors: Natalie E
authors: NE
authors: Patzlaff
authors: Ying
authors: Y
authors: Wang
authors: Sharon R
authors: SR
authors: Grady
authors: J Michael
authors: JM
authors: McIntosh
authors: Michael J
authors: MJ
authors: Marks
authors: Henry A
authors: HA
authors: Lester
authors: Ryan M
authors: RM
authors: Drenan
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*; D013477:Superior Colliculi / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D014795:Visual Pathways / Q000378:metabolism / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D011978:Receptors, Nicotinic; C104518:nicotinic receptor alpha6; D005680:gamma-Aminobutyric Acid; D004298:Dopamine