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Glutamate is the primary excitatory neurotransmitter in neurons and glia. N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate receptors are major ionotropic glutamate receptors. Glutamatergic neurotransmission is strongly linked with Ca 2+ homeostasis. Research has provided ample evidence that brain aging is associated with altered glutamatergic neurotransmission and Ca 2+ dysregulation. Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence. The current review examines Ca 2+ regulation with a focus on the NMDA receptors in the hippocampus. Integrating the knowledge of the complexity of age-related alterations in Ca 2+ homeostasis and NMDA receptor-mediated glutamatergic neurotransmission will positively shape the development of highly effective therapeutics to treat brain disorders including cognitive impairment.

Alteration in NMDA Receptor Mediated Glutamatergic Neurotransmission in the Hippocampus During Senescence