Glutamate receptors: Emerging links between subunit proteins and specific excitatory circuits in primate hippocampus and neocortex

Glutamate receptors (GluRs) are the primary mediators of excitatory neurotransmission in the CNS and play an indispensable role in brain function. Recent molecular advances have revealed an increasingly elaborate panel of GluR subunits that combine to form a variety of heteromeric GluR complexes with distinct functional characteristics determined by the stoichiometry of the subunit composition. Excitatory circuits in hippocampus and neocortex exhibit a complex and highly ordered array of termination patterns that reflect both segregation and convergence at specific target sites. We hypothesize that the molecular diversity of the GluRs will be manifested as circuit-specific profiles that will generate extensive functional diversity in cortical excitatory circuits. To elucidate the link between GluR diversity and neuroanatomical circuitry, immunocytochemical techniques employing subunit-specific antibodies have been used to localize various subunit proteins at the cellular and synaptic level. Such studies have revealed differential subunit parcellation between neocortical neuronal populations, as well as within defined dendritic compartments of hippocampal pyramidal cells. Additionally, the intradendritic parcellation of a specific GluR subunit is modifiable in an age-related and circuit-specific manner.