title: Cholinergic cells in the nucleus basalis of mice express the N-methyl-D-aspartate-receptor subunit NR2C and its replacement by the NR2B subunit enhances frontal and amygdaloid acetylcholine levels.
abstract: It is known that glutamatergic and cholinergic systems interact functionally at the level of the cholinergic basal forebrain. The N-methyl-d-aspartate receptor (NMDA-R) is a multiprotein complex composed of NR1, NR2 and/or NR3 subunits. The subunit composition of NMDA-R of cholinergic cells in the nucleus basalis has not yet been investigated. Here, by means of choline acetyl transferase and NR2B or NR2C double staining, we demonstrate that mice express both the NR2C and NR2B subunits in nucleus basalis cholinergic cells. We generated NR2C-2B mutant mice in which an insertion of NR2B cDNA into the gene locus of the NR2C gene replaced NR2C by NR2B expression throughout the brain. This NR2C-2B mutant was used to examine whether a subunit exchange in cholinergic neurons would affect acetylcholine (ACh) content in several brain structures. We found increased ACh levels in the frontal cortex and amygdala in the brains of NR2C-2B mutant mice. Brain ACh has been implicated in neuroplasticity, novelty-induced arousal and encoding of novel stimuli. We therefore assessed behavioral habituation to novel environments and objects as well as object recognition in NR2C-2B subunit exchange mice. The behavioral analysis did not indicate any gross behavioral alteration in the mutant mice compared with the wildtype mice. Our results show that the NR2C by NR2B subunit exchange in mice affects ACh content in two target areas of the nucleus basalis.
authors.affiliation: Institute of Physiological Psychology, Center for Biological and Medical Research, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: De Souza Silva
authors.forename: A
authors.initials: A
authors.lastname: Dolga
authors.forename: I
authors.initials: I
authors.lastname: Pieri
authors.forename: L
authors.initials: L
authors.lastname: Marchetti
authors.forename: U L M
authors.initials: UL
authors.lastname: Eisel
authors.forename: J P
authors.initials: JP
authors.lastname: Huston
authors.forename: E
authors.initials: E
authors.lastname: Dere
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D002799:Cholinergic Fibers / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism; D006185:Habituation, Psychophysiologic / Q000502:physiology*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D021122:Protein Subunits / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; C432823:NR2C NMDA receptor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D000109:Acetylcholine