AMPA-type receptors

Ultimately, changes in the activities of both NMDA- and AMPA-type receptors strengthen signal transmission across synapses, a phenomenon referred to as longterm potentiation (LTP). LTP appears to be critical for the development of manory and learning in both adults and children (Malinow and Malenka, 2002). However, LTP develops much more readily in children than in adults, at least in part because of the enhanced function of NMDA-type receptors in the developing brain (McDonald and Johnston, 1990 Crair and Malenka, 1995). 

Conversely, a new line of inquiry examined glutamatergic activity, not as a blocker of neurotransmission but as an agonist of AMPA type receptors. A new class of compounds, called ampakines, act as long-term boosters of the learning process, Aniracetam [206] is considered as the major product in this series. It improves performance in all classical behavioural tests in animal models. The question which has to be answered is whether these compounds simply have symptomatic effects on memory processes or whether they have complementary properties such as inhibition of cell death [207], Furthermore, certain compounds currently classed as ampakines such as oxiracetam and piracetam have not been shown to be effective in Alzheimer s disease. Others, such as nefiracetam (12) are in the animal experimentation stage and appear to be promising because of their impact on the neuronal cell adhesion molecules (NCAM) [208] and their effect on synapse plasticity. 

Kamiya Y, Andoh T, Furuya R, et al Comparison of the effects of convulsant and depressant barbiturate stereoisomers on AMPA-type glutamate receptors. Anesthesiology 90 1704-1713, 1999... 

Consistent with the notion that GLU is important in the behavioral effects of METH, compounds that block AMPA-type glutamatergic receptors (NBQX) 137 138 or NMDA receptors (NPC 12626)... 

Ampakines are drugs that potentiate currents mediated by AMPA-type glutamate receptors. In behavioral tests, ampakines are effective in correcting behaviors in various animal models of schizophrenia and depression. They protect neurons against neurotoxic insults, in part by mobilizing growth factors such as brain-derived neurotrophic factor (BDNF). 

Ohmori, J. Shimizu-Sasamata, O. Okada, M. Sakamoto, S. 8-(lH-Imida-zol-l-yl)-7-nitro-4(5H)-imidazo[l,2-a]quinoxalinone and Related Compounds Synthesis and Structure-Activity Relationships for the AMPA-type Non-NMDA Receptor, J. Med. Chem. 1997, 40, 2053. 

Furuyama, T., Kiyama, H., Sato, K., Park, H.T., Maeno, H., Takagi, H., Tohyama, M. Region-specific expression of subunits of ionotropic glutamate receptors (AMPA-type, KA-type, and NMDA receptors) in the rat spinal cord with special reference to nociception, Brain Res. Mol. Brain Res. 1993, 18, 141-151. 

Nicoll R. A., Tomita S., and Bredt D. S. (2006). Auxiliary subunits assist AMPA-type glutamate receptors. Science 311 1253-1256. 

Bernard V, Somogyi P, Bolam JP. Cellular, subcellular, and subsynaptic distribution of AMPA-type glutamate receptor subunits in the neostriatum of the rat. J Neurosci 1997 17 819-833. 

Suzuki T, Ito J, Takagi H, Saitoh F, Nawa H, et al. 2001. Biochemical evidence for localization of AMPA-type glutamate receptor subunits in the dendritic raft. Brain Res Mol Brain Res 89 20-28. 

Nakazawa, K., Mikawa, S., Hashikawa, T., and Ito, M. (1995). Transient and persistent phosphorylation of AMPA-type glutamate receptor subunits in cerebellar Purkinje... 

Tan, S. E., Wenthold, R. J., and Soderling, T. R. (1994). Phosphorylation of AMPA-type glutamate receptors by Ga" /calmodulin-dependent protein kinase II and PKG in cultured hippocampal neurons./. Neurosci. 14, 1123-1129. 

Baude A, Nusser Z, Molnar E, Mcllhinney RA, Somogyi P (1995) High-resolution immunogold localization of AMPA type glutamate receptor subunits at synaptic and non-synaptic sites in rat hippocampus. Neuroscience 69 1031-1055... 

Interestingly and consistent with previously reported results for prenatal TCDD exposure (another environmental contaminant found to be released as a result of the terrorist attack on the WTC) the effects on the aforementioned AMPA-mediated single cell responses were validated by RT-PCR. Glutamate receptor, AMPA-type subunit (GluRl) temporal developmental mRNA expression was determined in control and B(a)P-exposed offspring. The results shown in Figure 17.8 were normalized to ISsRNA expression. The results presented in this pre-weaning developmental... 

Retinal ganglion cells are the output cells of the refina. Their axons course along the vitreal surface of the refina and bundle together to exit the eye as the optic nerve. Ganglion cells are excited by glutamate released from bipolar cells acting on both NMDA and non-NMDA (KA- and AMPA-type) glutamate receptors (Thoreson and Witkovsky, 1999). 

ON and OFF responses of bipolar cells result from the presence of different glutamate receptors in the two cell types. OFF bipolar cells possess KA and AMPA-type ionotropic glutamate receptors, but not NMDA receptors (Thoreson and Witkovsky, 1999). Thus, like horizontal cells, the synapse from cones to OFF bipolar cells is sign-conserving, that is, light-evoked hyperpolarization of the cone reduces the depolarizing influence of AMPA/KA receptors thereby causing the OFF bipolar cell to hyperpolarize. 

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