Differential expression of five N‐methyl‐D‐aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats

Abstract

Five N-methyl-D-aspartate (NMDA) receptor subunits have been identified thus far: NR1, NR2A, NR2B, NR2C, and NR2D. Here, we have analyzed the expression patterns of mRNAs for the NMDA receptor subunits in the developing and adult rats by in situ hybridization. The developmental changes of the expression patterns were most salient in the cerebellum. In the external granular layer, hybridization signals of mRNAs for NR1, NR2A, NR2B, and NR2C appeared by postnatal day 3, but no NR2D mRNA was expressed at any developmental stage examined. The NR1 mRNA was expressed in all cerebellar neurons at all developmental stage examined. The NR1 mRNA was expressed in all cerebellar neurons at all developmental stages examined. The signals for the NR2A mRNA appeared in Purkinje cells and granule cells during the second postnatal week. The signals for the NR2B mRNA in granule cells were seen transiently during the first 2 weeks after birth. The signals for NR2C mRNA appeared in granule cells and glial cells during the second postnatal week. The signals for NR2D mRNA appeared transiently in Purkinje cells during the first 8 postnatal days; in adult rats, these were seen in stellate and Golgi cells. In the cerebellar nuclei, mRNAs for NR1, NR2A, NR2B, and NR2D were more or less expressed on postnatal day 0, while expression signals for the NR2C mRNA were first detected in postnatal day 14. Thus, the most conspicuous changes of expression patterns were observed in the cerebellar cortex during the first 2 weeks after birth, when development and maturation of the cerebellum proceed most rapidly.

A pivotal role of calcineurin signaling in development and maturation of postnatal cerebellar granule cells

“…Interestingly, the FK-up genes include many neurotransmitter receptors, ion channels, and transporters. The GABA A ␣1, GABA A ␣6, and GABA A ␦ subunits of GABA receptors, the NR2C subunit of NMDA receptors, the TASK-1 channel, and the KCC2 transporter have been shown to be highly expressed in mature granule cells (21,22,24,25). The CaN signaling thus coordinately controls the expression of fundamental components in synaptic transmission of postmigratory granule cells and may contribute to the maturation and refinement of cerebellar circuit formation.…”

“…A few of the FK-up genes, including NR2C, GABA A ␣1, GABA A ␣6, GABA A ␦, Wnt7a, Tiam1, TASK-1, and KCC2 genes, have been shown to be predominantly expressed in the IGL and up-regulated in the cerebellum during postnatal development (5,(21)(22)(23)(24)(25). In contrast, doublecortin, Homer2, MARCKS-like protein, caspase-3, and VGluT2 genes, which are all FK-down genes, have been reported to be significantly expressed in the EGL during the postnatal period (26)(27)(28)(29)(30).…”

NMDA Receptor Heterogeneity During Postnatal Development of the Rat Brain: Differential Expression of the NR2A, NR2B, and NR2C Subunit Proteins

“…NR2A, 2B, and 2C (summarized in Table I). Neuro-2) (Akazawa et al, 1994;Monyer et al, 1994; Watatransmission involving NMDA receptors is mediated nabe et al, 1994), the NR2A protein was predomimainly by receptors containing the NR2B subunit in nantly located in the molecular layer. An immunohisneonatal rat brain, but a substantial reorganization tochemical study using a nonselective NR2A/2B antitakes place within 3 weeks after birth.…”

Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

“…7 and 8a). Given that Purkinje cells are thought to express relatively low amounts of functional NMDA receptors [4,21] and that only CF but not PF stimulation could induce an NMDA receptor current in PNs of adult rodents [32,34], while molecular layer interneurons are known for a rich expression of NMDA receptors [1,9], we propose that interneurons are the most likely source of NO for preLTP [33,39] and of endocannabinoids [6] for pre LTD. Of course, we cannot exclude that 4 Hz PF stimulation also activates NMDA and/or mGlu1 receptors on PNs to some degree resulting in some release of endocannabinoids. If the LTD observed in PNs that were patch-clamped with a high concentration of a Ca 2+ chelator (30 mM BAPTA) in the intracellular solution (Figs.…”