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Heterogeneity and Selective Targeting of Neuronal Nicotinic Acetylcholine Receptor (nAChR) Subtypes Expressed on Retinal Afferents of the Superior Colliculus and Lateral Geniculate Nucleus: Identification of a New Native nAChR Subtype 32(5 or 3) Enriched in Retinocollicular Afferents

CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Medical Pharmacology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy (C.G., M.M., A.G., F.C.); Department of Biomedical Sciences, Section of Physiology, University of Modena and Reggio Emilia, Modena, Italy (A.Z., M.Z.); Laboratoire de Neurobiologie Moléculaire, Centre National de la Recherche Scientifique Unité de Recherche Associée 2182 "Récepteurs et Cognition", Institut Pasteur, Paris, France (N.C., J.-P.C.); and Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado (P.W., M.J.M.)

The activation of neuronal nicotinic acetylcholine receptors (nAChRs) has been implicated in the activity-dependent development and plasticity of retina and the refinement of retinal projections. Pharmacological and functional studies have also indicated that different presynaptic nAChRs can have a modulatory function in retinotectal synapses. We biochemically and pharmacologically identified the multiple nAChR subtypes expressed on retinal afferents of the superior colliculus (SC) and lateral geniculate nucleus (LGN). We found that the 62^* and 4(non6)2^* nAChRs are the major receptor populations expressed in both SC and LGN. In addition, the LGN contains two minor populations of 262^* and 32^* subtypes, whereas the SC contains a relatively large population of a new native subtype, the 32(5/3) nAChR. This subtype binds the -conotoxin MII with an affinity 50 times lower than that of the native 62^* subtype. Studies of tissues obtained from eye-enucleated animals allowed the identification of nAChRs expressed by retinal afferents: in SC 62^*, 462^*, and 32^* (approximately 45, 35, and 20%, respectively), in LGN, 462^*, 62^*, 42^*, 262^*, and 32^* (approximately 40, 30, 20, 5, and 5%, respectively). In both regions, more than 50% of nAChRs were not expressed by retinal afferents and belonged to the 42^* (90%) or 452^* (10%) subtypes. Moreover, studies of the SC tissues obtained from wild-type and 4, 6, and 3 knockout mice confirmed and extended the data obtained in rat tissue and allowed a comprehensive dissection of the composition of nAChR subtypes present in this retinorecipient area.

Received for publication June 21, 2005.

Accepted for publication July 27, 2005.

Address correspondence to: Dr. Cecilia Gotti, CNR, Institute of Neuroscience, Section of Cellular and Molecular Pharmacology Center, Department of Medical Pharmacology, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy. E-mail: c.gotti{at}in.cnr.it

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