Expression of N-Methyl-D-Aspartate receptor subunit mRNAs in the human brain: Striatum and globus pallidus

Abstract

N-methyl-D-aspartate receptors (NRs) play an important role in basal ganglia function. By using in situ hybridization with ribonucleotide probes, we investigated the regional and cellular distribution of NR subunit mRNA expression in the human basal ganglia: caudate nucleus, putamen, lateral globus pallidus (LGP), and medial globus pallidus (MGP). Analysis of both film autoradiograms and emulsion-dipped slides revealed distinct distribution patterns for each subunit. On film autoradiograms, the signal for NR1, NR2B, and NR2C in the striatum (STR) was higher than in globus pallidus (GP). The NR2D probe gave a stronger signal in GP than in STR. For NR2A we found a signal in all regions. Analysis of emulsion-dipped sections demonstrated that in striatal neurons, the NR2B signal was higher than in GP neurons. In GP neurons, NR2D was more abundant than in striatal neurons. Despite the relatively low signal on film for NR2C in GP, we found a slightly higher signal in GP per neuron than in STR since in the pallidal areas neurons were sparse but intensely labeled. NR1 and NR2A were more evenly distributed over neurons of STR and GP Between the different parts of STR and GP, we observed only minor differences in the expression of NRs. In MGP a subpopulation of neurons exhibiting low NR2D signals could be separated from the majority of neurons showing an intense NR2D signal. Since the physiological properties of NRs are dependent on subunit composition, these data suggest a high degree of regional specialization of NR properties in the human basal ganglia.

Developmental alterations of DHPG-induced long-term depression of corticostriatal synaptic transmission: switch from NMDA receptor-dependent towards CB1 receptor-dependent plasticity

“…In adult medium spiny neurons, the predominant NR2 subunits are NR2A and NR2B [21,32,57]. In the rat brain, the NR2B subunit is highly expressed in all regions already in neonates but becomes gradually restricted to the forebrain during maturation, while the expression of the NR2A subunit increases during the first three postnatal weeks, becoming prevailing in the adult brain [67].…”

Changes in NMDA receptor subunit gene expression in the rat brain following withdrawal from forced long-term ethanol intake

“…Other studies did not reveal alterations of NR2A mRNA expression in mouse brain (Snell et al 1996) and in cultured cortical neurons (Hu et al 1996) chronically treated with ethanol. The NR2A subunit is known as the antagonist-preferring type of NR subunits (Kosinski et al 1998). Thus, upregulation of this subunit by withdrawal of ethanol may result from its earlier chronic inhibition.…”

Localization of alternatively spliced NMDAR1 glutamate receptor isoforms in rat striatal neurons

“…NMDA receptor subunit messenger RNAs and proteins are abundant in the striatum (Petralia et al, 1994;Standaert et al, 1994;Kosinski et al, 1998), where the receptors serve a variety of functions. Striatal NMDA receptors are involved in the regulation of ␥-aminobutyric acid (GABA), neuropeptide, and acetylcholine release (Damsma et al, 1991;Ruzicka and Jhamandas, 1991;Young and Bradford, 1991;Bustos et al, 1992;Galli et al, 1992;Somers and Beckstead, 1992;Morari et al, 1993;Young and Bradford, 1993), and their activation stimulates the expression of the immediate-early genes c-fos and c-jun (Xia et al, 1996;Berretta et al, 1997).…”