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

Mackey, Elisha D. W. and Engle, Staci E. and Kim, Mi Ran and O'Neill, Heidi C. and Wageman, Charles R. and Patzlaff, Natalie E. and Wang, Ying and Grady, Sharon R. and McIntosh, J. Michael and Marks, Michael J. and Lester, Henry A. and Drenan, Ryan M. (2012) α6* Nicotinic Acetylcholine Receptor Expression and Function in a Visual Salience Circuit. Journal of Neuroscience, 32 (30). pp. 10226-10237. ISSN 0270-6474. PMCID PMC3432940. doi:10.1523/JNEUROSCI.0007-12.2012.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle
Lester, Henry A.0000-0002-5470-5255
Drenan, Ryan M.0000-0002-8141-8577
Additional Information:© 2012 The Authors. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( Received Jan. 2, 2012; revised April 14, 2012; accepted May 14, 2012. Author contributions: E.D.W.M., H.C.O., S.R.G., M.J.M., and R.M.D. designed research; E.D.W.M., S.E.E., M.R.K., H.C.O., C.R.W., N.E.P., Y.W., S.R.G., M.J.M., and R.M.D. performed research; Y.W. contributed unpublished reagents/ analytic tools; E.D.W.M., S.E.E., M.R.K., H.C.O., Y.W., S.R.G., M.J.M., H.A.L., and R.M.D. analyzed data; E.D.W.M., S.R.G., J.M.M., M.J.M., H.A.L., and R.M.D. wrote the paper. This work was supported by NIH Grants DA030396, DA17279, DA12242, DA015663, DA03194, MH53631, and GM48677. Thanks to the Purdue Histology and Phenotyping Laboratory (Purdue University, School of Veterinary Medicine) for technical assistance with histology procedures. The authors declare no competing financial interests.
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Issue or Number:30
PubMed Central ID:PMC3432940
Record Number:CaltechAUTHORS:20120904-085001085
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:33814
Deposited By: Jason Perez
Deposited On:06 Sep 2012 20:49
Last Modified:09 Nov 2021 23:04

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