Memory consolidation induces N-methyl-D-aspartic acid-receptor- and Ca2+/calmodulin-dependent protein kinase II-dependent modifications in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor properties.
The N-methyl-D-aspartic acid (NMDA) receptor-dependent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) is necessary for induction of the long-term potentiation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated responses in the CA1 region of the hippocampus, a putative model for learning and memory. We analyzed the interplay among NMDA receptor, CaMKII and AMPA receptor during consolidation of the memory for an inhibitory avoidance learning task in the rat. Bilateral intra-CA1 infusion of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (AP5) or of the CaMKII inhibitor 2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)] amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) (KN-93) immediately after step-down inhibitory avoidance training hindered memory consolidation. Learning of the avoidance response induced the NMDA receptor-dependent translocation of alphaCaMKII to a postsynaptic density-enriched fraction isolated from dorsal CA1 and the autophosphorylation of this kinase at Thr-286. Step-down inhibitory avoidance training increased the quantity of GluR1 and GluR2/3 AMPA receptor subunits and the phosphorylation of GluR1 at Ser-831 but not at Ser-845 in CA1 postsynaptic densities. The intra-CA1 infusion of KN-93 and AP5 blocked the increases in GluR1 and GluR2/3 levels and the phosphorylation of GluR1 brought on by step-down inhibitory avoidance training. Our data suggest that step-down inhibitory avoidance learning promotes the learning-specific and NMDA receptor-dependent activation of CaMKII in the CA1 region of the dorsal hippocampus and that this activation is necessary for phosphorylation and translocation of AMPA receptor to the postsynaptic densities, similarly to what happens during long-term potentiation.
Bevilaqua
L R
LR
Laboratorio de Neuroreceptores, Instituto de Biología Celular y Neurociencias Prof. Dr. Eduardo de Robertis, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 3 Piso, Ciudad Autónoma de Buenos Aires, CP 1121 Argentina.
Medina
J H
JH
Izquierdo
I
I
Cammarota
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D015151:Immunoblotting; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
D015763:2-Amino-5-phosphonovalerate; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides; C104722:glutamate receptor ionotropic, AMPA 2