NMDA receptors (NMDARs) play a distinct role at excitatory glutamatergic synapses, where they are usually localized with other ionotropic glutamate receptors, including tors. Two features are essential to their specialized roles in synaptic plasticity and the excitodependent magnesium block, the removal of which requires depolarization of the membrane potential. Second, upon activation, the NMDAR channel passes sodium and, importantly, calcium into the neuron. Calcium is the universal second messenger in numerous intracellular signaling cascades and is critical in synaptic plasticity and mechanisms of neurotoxicity (288).