Differential effect of glutamate receptor blockade on dendritic outgrowth in chicken lumbar motoneurons

Glutamate receptor-mediated changes in intracellular Ca(2+) may have important implications for activity-dependent regulation of early embryonic development. NMDA receptors were originally considered to be the sole source of glutamate-mediated Ca(2+) influx. However, AMPA receptors lacking the GluR2 subunit also allow a significant influx of Ca(2+) ions. Although Ca(2+)-permeable AMPA receptors are a familiar feature in developing neurons, the developmental function of these receptors during the formation of the nervous system remains to be established. Previously, we have demonstrated that chicken lumbar motoneurons express Ca(2+)-permeable AMPA receptors at embryonic day (E) 6. The Ca(2+) permeability of AMPA receptors decreases three-fold by E11. In this study we explored the role of transiently expressed Ca(2+)-permeable AMPA receptors in regulating the dendritic morphology of developing motoneurons in ovo. The AMPA receptor blocker CNQX (1 mg/day), when applied between E5 and E8, causes a significant increase in dendritic outgrowth and branching as compared with vehicle-treated embryos. Inhibition of NMDA receptor activity with MK-801 (100 microg/day) during this period has no effect on dendritic morphology. Treatment of chicken embryos with CNQX between E8 and E11 (when most receptors become Ca(2+)-impermeable) has no significant effect on dendritic morphology. However, MK-801 application between E8 and E11 causes a significant reduction in dendritic length and branching. These findings indicate that AMPA receptor activation between E5 and E8 limits dendritic outgrowth in developing motoneurons, whereas NMDA receptor activation is involved in dendritic remodeling after the establishment of synaptic contacts with sensory afferents.