The amino acid glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS). Therefore, it is not surprising that glutamate receptors are located throughout the brain (see Fig. 1 for glutamatergic projections). In addition, given the ubiquitous distribution of glutamate and its receptors, its function as the primary excitatory neurotransmitter is crucial for many processes, especially those mediating neuroplasticity, learning and memory.31–33 Glutamate interacts with both metabotropic mGlu1–mGlu8 (Grm1–Grm8 = mGluR1–mGluR8) and ionotropic receptors, which include those that can bind to N-methyl-D-aspartate (NMDA) (subunits: GluN1 (Grin1 = NR1); GluN2a–GluN2d (Grin2a–Grin2d = Nr2a–Nr2d); GluN3a–GluN3b (Grin3a–Grin3b = NR3a–NR3b), those that can bind to α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subunits: GluA1–GluA4 (Gria1–Gria4 = GluR1–GluR4) or kainite subunits GluK1–GluK4 (Grik1–Grik4 = GluR5–GluR7 + KA1–KA2); these nomenclatures reflect IUPHAR, HUGO, and “old” symbols respectively.34–36 Due to glutamate’s role in excitotoxicity, extracellular glutamate must be tightly controlled.34,37,38 This is accomplished, for the most part, by multiple glutamate transporters.34 The human excitatory amino acid transporter 2 (EAAT2) and its rodent analog glutamate transporter 1 (GLT1) appear to be the main transporters performing this function centrally.34,37
