Modulation of Neuronal Migration by NMDA Receptors

TLDR

The NMDA subtype of the glutamate receptor is essential for neuronal differentiation and synapse formation or elimination during brain development. Blockade of NMDA receptors curtails granule cell migration, while removal of magnesium, glycine application, or inhibition of glutamate uptake enhances migration rates. These findings indicate that NMDA receptor activity regulates granule cell migration and may play an early calcium‑dependent role before neurons reach their targets and form synapses.

Abstract

The N -methy -D-aspartate (NMDA) subtype of the glutamate receptor is essential for neuronal differentiation and establishment or elimination of synapses in a developing brain. The activity of the NMDA receptor has now been shown to also regulate the migration of granule cells in slice preparations of the developing mouse cerebellum. First, blockade of NMDA receptors by specific antagonists resulted in the curtailment of cell migration. Second, enhancement of NMDA receptor activity by the removal of magnesium or by the application of glycine increased the rate of cell movement. Third, increase of endogenous extracellular glutamate by inhibition of its uptake accelerated the rate of cell migration. These results suggest that NMDA receptors may play an early role in the regulation of calcium-dependent cell migration before neurons reach their targets and form synaptic contacts.