期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：41
页码：15991-15996
DOI：10.1073/pnas.0807635105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Acetylcholine (ACh) is a known modulator of the activity of dopaminergic (DAergic) neurons through the stimulation of nicotinic ACh receptors (nAChRs). Yet, the subunit composition and specific location of nAChRs involved in DA-mediated locomotion remain to be established in vivo. Mice lacking the {beta}2 subunit of nAChRs ({beta}2KO) display striking hyperactivity in the open field, which suggests an imbalance in DA neurotransmission. Here, we performed the selective gene rescue of functional {beta}2*-nAChRs in either the substantia nigra pars compacta (SNpc) or the ventral tegmental area (VTA) of {beta}2KO mice. SNpc rescued mice displayed normalization of locomotor activity, both in familiar and unfamiliar environments, whereas restoration in the VTA only rescued exploratory behavior. These data demonstrate the dissociation between nigrostriatal and mesolimbic {beta}2*-nAChRs in regulating unique locomotor functions. In addition, the site-directed knock-down of the {beta}2 subunit in the SNpc by RNA interference caused hyperactivity in wild-type mice. These findings highlight the crucial interplay of nAChRs over the DA control of spontaneous locomotion.
关键词：dopaminergic systems ; gene rescue ; lentiviral vector ; RNAi
