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Title: Triheteromeric N-methyl-D-aspartate receptors differentiate synaptic inputs onto pyramidal neurons in somatosensory cortex: involvement of the GluN3A subunit. Author: Pilli J, Kumar SS. Journal: Neuroscience; 2012 Oct 11; 222():75-88. PubMed ID: 22814002. Abstract: N-methyl-D-aspartate receptors (NMDARs) are glutamatergic by virtue of glutamate-binding GluN2 subunits and glycinergic by virtue of glycine-binding GluN1 and GluN3 subunits. The existence, location, and functional-significance of NMDARs containing both GluN2 and GluN3 subunits have as yet remained unelucidated. Here we report on the discovery and characterization of a novel type of NMDARs, found at layer (L)1/primary whisker-motor-cortex inputs onto L5 pyramidal neurons in somatosensory cortex, that are distinct in structure and function from conventional GluN2A-containing NMDARs at thalamic/striatal (Str) inputs onto the same neurons. These receptors had a threshold-like activation at hyperpolarized holding-potentials with strong outward rectification of their current-voltage relationships unlike any known GluN1/GluN2-containing NMDARs. Pharmacology revealed a triheteromeric-receptor with features common to glutamate-activated GluN1/GluN2-containing and glycine-activated GluN1/GluN3-containing diheteromeric NMDARs. However, unlike GluN1/GluN3 receptors, NMDARs at L1 inputs were activated by glutamate and blocked by d-AP5, Ca(2+)-permeable, and more efficient at integrating and potentiating EPSPs selectively over Str inputs during high-frequency stimulation while obviating the need for AMPAR-mediated depolarization.[Abstract] [Full Text] [Related] [New Search]