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, noveltyinduced 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.

Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors

“…The main afferent inputs into the basal forebrain are glutamatergic projections from the ventral tegmental area [45], GABAergic axons from the nucleus accumbens [46] and cholinergic projections from the pons [47]. There are also afferents from cortical, amygdaloid, striatal neurons.…”

The Basal Forebrain Cholinergic Projection System in Mice

“…ACh can activate nicotinic or G-protein coupled muscarinc receptors. Finally, basal forebrain cholinergic neurons in rodents express several neurotransmitter receptors, including adrenergic, glutamatergic, GABAergic (De Souza Silva et al, 2006;Kiss et al, 1993;Zaborszky et al, 2004), receptors for estrogen and endocannabinoids (Harkany et al, 2003). The synthesis and release of ACh requires the expression of three genes, encoding ChAT, the vesicular acetylcholine transporter (VAChT) and the choline transporter 1 (Brandon et al, 2004;Ferguson et al, 2003).…”

Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate

“…BF receives glutamatergic innervations from various areas, including the cortex, the amygdala and some regions of the brain stem (Fuller et al ., ; Sarter and Bruno, ). Glutamate (GLUT) receptors are expressed in the BF (De Souza Silva et al ., ; Martin et al ., ), and local application of GLUT agonists into the BF results in EEG activation, W enhancement (Cape and Jones, ; Manfridi et al ., ; Wigren et al ., ) and an increase in cortical acetylcholine release. The amount of acetylcholine released correlates with the gamma power in the EEG, indicating that BF cholinergic neurones may participate in the mediation of arousal (Fournier et al ., ).…”