NMDARs

NMD A receptors are selectively activated by A/-methyl-D-aspartate (NMD A) (182). NMD A receptor activation also requires glycine or other co-agonist occupation of an allosteric site. NMDAR-1, -2A, -2B, -2C, and -2D are the five NMD A receptor subunits known. Two forms of NMDAR-1 are generated by alternative splicing. NMDAR-1 proteins form homomeric ionotropic receptors in expression systems and may do so m situ in the CNS. Functional responses, however, are markedly augmented by co-expression of a NMDAR-2 and NMDAR-1 subunits. The kinetic and pharmacological properties of the NMD A receptor are influenced by the particular subunit composition. 

Monyer H, Jonas P, Rossier J (1999) Molecular determinants controlling functional properties of AMPARs and NMDARs in the mammalian CNS, chapter 9 Ionotropic glutamate receptors in the CNS. Springer Verlag... 

Orexin neurons, likely to be glutamatergic themselves, express the excitatory amino acid transporter EAAT3, vesicular glutamate transporters VGLUT1 and VGLUT2, secretogranin II, ionotropic (NMDAR,... 

NMDAR. An ionotropic receptor for glutamate. It plays a critical role in synaptic plasticity mechanisms and thus is necessary for several types of learning and memory. 

The distribution of NMDAR subtypes offers one explanation for regional brain vulnerability to HIV-associated injury. Neonatal brain predominantly expresses... 

Thus, the mechanistic properties of the NMDA receptor can help account for the properties of temporal specificity, cooperativity, and associativity of LTP. They can also explain why both high-frequency stimulation (100 Hz) and pairing low-frequency stimulation with postsynaptic depolarization can induce LTP. The occurrence of presynaptic activity followed by postsynaptic activity determines a temporal sequence and specificity. To generate sufficient depolarization in the postsynaptic cell to expel Mg2+ from NMDAR channels usually requires cooperative depolarization at many synapses. Moreover, the requirement of postsynaptic depolarization also underlies associativity since the depolarization caused by the strongly activated synapses can relieve the Mg2+ blockade of the NMDA receptors on weakly activated synapses. 

Alcohol GABAaR, 5-HT3R, nAChR, NMDAR, Kir3 channels Excitation, disinhibition ( ) 3... 

HTxR, serotonin receptor CB1R, cannabinoid-1 DAT, dopamine transporter GABA, y-aminobutyric acid Kir3 channels, G protein-coupled inwardly rectifying potassium channels LSD, lysergic acid diethylamide i -OR, H-opioid receptor nAChR, nicotinic acetylcholine receptor NET, norepinephrine transporter NMDAR, N -methyl-D-aspartate receptor SERT, serotonin transporter VMAT, vesicular monoamine transporter indicates data not available. 

Sobolevsky, A. I., Beck, C., Wollmuth, L. P. Molecular rearrangements of the extracellular vestibule in NMDAR channels during gating, Neuron 2002, 33, 75-85. 

Zimmer, M., Fink, T. M., Franke, Y., Lichter, P., Spiess, J. Cloning and structure of the gene encoding the human NMDA receptor (NMDAR-1), Gene 1995, 159, 219-223. 

NR1 is a component of all native NMDA receptors. The NRI subunit is the glycine binding subunit. It exists as 8 splice variants of a single gene. C-terminal deletion of the NRI subunit causes NMDAR inactivation, changes in downstream... 

CA-CREB had some effects similar to CA-CaMKIV such as a dramatic increase in the magnitude and maintenance of LTP (late phase), as well as increased excitatory currents mediated by the NMDAR. However, there were some effects that were different including increased excitatory currents initiated by the AMPAR, which were observed in CA-CaMKIV treated animals only (Marie et al., 2005). Therefore, it was concluded that the effects of CaMKIV on LTP mediated by NMDARs correlated with CREB phosphorylation, whereas the effects of CaMKIV mediated by AMPARs must involve some target of CaMKIV other than CREB. Also, some defects in the early phase of LTP in Camk4, / mice were seen as early as 5 min after stimulation which is much too early for any new gene transcription to be causally relevant (Ho et al., 2000). 

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