A glycine receptor antagonist, strychnine, blocked NMDA receptor activation in the neonatal mouse neocortex

The NMDA receptor (NMDAR) is a Ca-permeable cation channel that plays a critical role in neural network formation during brain development. Since it is blocked in a voltage-dependent manner by extracellular Mg, in order for the NMDA to be activated, the membrane must be strongly depolarized. Immature neurons in the developing neocortex can be depolarized by ligand-gated Cl channels, such as the glycine receptor (GlyR) or GABAA receptor (GABAAR). We here assess the contribution of GlyRs to Ca influx via NMDARs in neonatal mouse cortical neurons. The GlyR antagonist, strychnine, was more effective in suppressing postsynaptic Ca influx than the GABAAR antagonist, picrotoxin, suggesting greater potentiation of NMDARs by GlyRs than by GABAARs. The GlyR, known to be endogenously activated at this stage, may play a critical role in neocortical development.