Distinct spatiotemporal expressions of five NMDA receptor channel subunit mRNAs in the cerebellum

The distribution of five NMDA receptor channel subunit mRNAs was examined in the mouse cerebellum from embryonic day 13 through postnatal day 56, by in situ hybridization with subunit-specific oligonucleotide probes. At postnatal days 21 and 56, each cerebellar neuron displayed differential expressions of the epsilon subunit mRNAs. The granule cells showed hybridizing signals for the epsilon 1 and epsilon 3 subunit mRNAs, the molecular layer neurons for the epsilon 4 subunit mRNA, and the cerebellar nucleus neurons for the epsilon 1 and epsilon 4 subunit mRNAs, whereas the Purkinje cells did not express any epsilon subunit mRNAs. At early postmitotic stages of development, the epsilon 2 subunit mRNA appeared in each cerebellar neuron, including the Purkinje cells, and the epsilon 4 subunit mRNA appeared in neurons of the molecular layer and the cerebellar nuclei. The expression patterns in the cerebellum altered drastically during the first 2 postnatal weeks; the epsilon 1 and epsilon 3 subunit mRNAs appeared in the granule cells and the cerebellar nucleus neurons, whereas the epsilon 2 subunit mRNA disappeared from each neuron and the signal levels of the epsilon 4 subunit mRNA decreased remarkably. In contrast to the differential expressions of the four epsilon subunit mRNAs, intense signals for the zeta 1 subunit mRNA were observed in each cerebellar neuron from early postmitotic stages through the mature stage. These findings suggest that anatomical organization of the epsilon subunits is heterogeneous in the cerebellum both spatially and temporally, which would give rise to functional diversity of the NMDA receptor channel.