Differential distribution of group I metabotropic glutamate receptors in developing human cortex

Neuronal and glial cells in human cerebral cortex are enriched in group I metabotropic glutamate receptors (mGluRs). Developmental regulation of mGluRs has been shown in rodent brain and recent studies suggest an involvement of mGluR-mediated glutamate signaling in the proliferation and survival of neural progenitor cells. In the present study, we have investigated the expression and cell-specific distribution of group I mGluRs (mGluR1alpha and mGluR5) during prenatal human cortical development. mGluR5 was expressed in developing human cortex from the earliest stages tested (9 gestational weeks, GW), with strong expression in the ventricular/subventricular zones. mGluR1alpha immunoreactivity (IR) was observed in the cortical plate at 13GW and persisted throughout the prenatal development. Both receptors were expressed in pyramidal neurons in the first postnatal year. Group I mGluRs were also expressed by reelin-positive Cajal-Retzius cells present in the marginal zone/layer I of the developing cortex. mGluR5 IR in these cells was observed in the earliest developmental stages and persisted during the early postnatal period. In contrast, mGluR1alpha IR was detected in Cajal-Retzius cells during the late phase of prenatal development. These findings show a differential expression pattern of group I mGluR subtypes, suggesting a role for both receptors in the early stages of corticogenesis with, however, a different contribution to human cortical developmental events.