Interplay of beta2* nicotinic receptors and dopamine pathways in the control of spontaneous locomotion.
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 beta2 subunit of nAChRs (beta2KO) display striking hyperactivity in the open field, which suggests an imbalance in DA neurotransmission. Here, we performed the selective gene rescue of functional beta2*-nAChRs in either the substantia nigra pars compacta (SNpc) or the ventral tegmental area (VTA) of beta2KO 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 beta2*-nAChRs in regulating unique locomotor functions. In addition, the site-directed knock-down of the beta2 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.
Avale
Maria Elena
ME
Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Unité de Recherche Associée 2182, Centre National de la Recherche Scientifique, Institut Pasteur, F75724 Paris Cedex 15, France.
Faure
Philippe
P
Pons
Stéphanie
S
Robledo
Patricia
P
Deltheil
Thierry
T
David
Denis J
DJ
Gardier
Alain M
AM
Maldonado
Rafael
R
Granon
Sylvie
S
Changeux
Jean-Pierre
JP
Maskos
Uwe
U
D000818:Animals; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D005106:Exploratory Behavior; D006948:Hyperkinesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D020239:Receptor Cross-Talk; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D013378:Substantia Nigra; D017557:Ventral Tegmental Area
D004298:Dopamine; D011978:Receptors, Nicotinic