Modified N-methyl-D-aspartate receptor subunit expression emerges in reeler Purkinje cells after accomplishment of the adult wild-type expression.

In terms of gene expression for the N-methyl-D-aspartate (NMDA) receptor channel subunits, the adult reeler cerebellum contains two Purkinje cell populations, one expressing the zeta 1 subunit mRNA (wild-type expression) and another expressing the epsilon 1 and zeta 1 subunit mRNAs (modified expression). To clarify development of these two populations, in situ hybridization analysis was performed in the reeler cerebellum from birth to 1 year of age. The epsilon 1 subunit mRNA was not detected in any Purkinje cell clusters (PCCs) until postnatal day 21 (P21). Additional signals for the epsilon 1 subunit mRNA first appeared at P56 in a subset of PCCs, and persisted until 1 year of age. The epsilon 2 and epsilon 4 subunit mRNAs were transiently expressed in PCCs at birth, and disappeared thereafter. No signals for the epsilon 3 subunit mRNA was detected in PCCs at any postnatal stages examined. The zeta 1 subunit mRNA was expressed in all PCCs from birth through 1 year. When compared with the wild-type Purkinje cells, reeler Purkinje cells with modified expression are thus differentiated from those once accomplished the adult wild-type expression (the zeta 1 subunit alone) by down-regulation of the epsilon subunits. The present results further indicate that the onset of the modified expression is subsequent to the establishment of synaptic connectivities in the cerebellum.