My dissertation research seeks to better understand the physiology, biophysics, and pharmacology of N-methyl-D-aspartate receptors (NMDARs) from a molecular to circuit level. These ligand-gated neurotransmitter receptors play important roles in learning, memory, and cognition, and their dysfunction is implicated in many neurological and psychiatric disorders. I employ cell-attached voltage patch clamp electrophysiology techniques to study the changes in receptor gating from patient-derived missense mutations in the GRIN1 gene, which encodes the obligatory GluN1 subunit of these receptors. After characterizing their gating mechanisms, I perfuse NMDAR allosteric modulators to try and recover variant receptor activity. I also use ex-vivo rodent brain slice electrophysiology techniques in a whole-cell configuration to investigate how low-dose ketamine, an NMDAR antagonist, alters excitation and inhibition balance in the prefrontal cortex, which may have implications in its actions as a rapid-acting antidepressant.