Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression.
It is widely believed that long-term depression (LTD) and its counterpart, long-term potentiation (LTP), involve mechanisms that are crucial for learning and memory. However, LTD is difficult to induce in adult cortex for reasons that are not known. Here we show that LTD can be readily induced in adult cortex by the activation of NMDA receptors (NMDARs), after inhibition of glutamate uptake. Interestingly there is no need to activate synaptic NMDARs to induce this LTD, suggesting that LTD is triggered primarily by extrasynaptic NMDA receptors. We also find that de novo LTD requires the activation of NR2B-containing NMDAR, whereas LTP requires activation of NR2A-containing NMDARs. Surprisingly another form of LTD, depotentiation, requires activation of NR2A-containing NMDARs. Therefore, NMDARs with different synaptic locations and subunit compositions are involved in various forms of synaptic plasticity in adult cortex.
Massey
Peter V
PV
Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD, United Kingdom.
Johnson
Benjamin E
BE
Moult
Peter R
PR
Auberson
Yves P
YP
Brown
Malcolm W
MW
Molnar
Elek
E
Collingridge
Graham L
GL
Bashir
Zafar I
ZI
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003998:Dicarboxylic Acids / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D021122:Protein Subunits; D011759:Pyrrolidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D015763:2-Amino-5-phosphonovalerate; D001224:Aspartic Acid; D003998:Dicarboxylic Acids; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016202:N-Methylaspartate; D014179:Neurotransmitter Uptake Inhibitors; D010636:Phenols; D010852:Picrotoxin; D010880:Piperidines; D021122:Protein Subunits; D011759:Pyrrolidines; D011810:Quinoxalines; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C498554:5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; C109643:Ro 25-6981; C120673:benzyloxyaspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C083486:pyrrolidine-2,4-dicarboxylic acid; C010739:ifenprodil