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

The NMDA receptor (NMDAR) is a Ca²⁺-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 Mg²⁺, 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 GABA_A receptor (GABA_AR). We here assess the contribution of GlyRs to Ca²⁺ influx via NMDARs in neonatal mouse cortical neurons. The GlyR antagonist, strychnine, was more effective in suppressing post-synaptic Ca²⁺ influx than the GABA_AR antagonist, picrotoxin, suggesting greater potentiation of NMDARs by GlyRs than by GABA_ARs. The GlyR, known to be endogenously activated at this stage, may play a critical role in neocortical development.