title: Close linkage between calcium/calmodulin kinase II alpha/beta and NMDA-2A receptors in the lateral amygdala and significance for retrieval of auditory fear conditioning.
abstract: The general mechanism underlying memory and learning is an area under intense investigation and debate, yet this mechanism still remains elusive. Auditory fear conditioning (when a tone is paired with a foot shock) is a simple associative form of learning for which many mechanistic details are known. Lesions of the lateral/basolateral nuclei of the amygdala result in the selective impairment of fear conditioning, indicating that this is a key region for this type of learning. Fear conditioning induces a lasting synaptic potentiation in the lateral nuclei of the amygdala. In addition, recent results from several laboratories suggest that N-methyl-D-aspartate (NMDA) receptor activation in the amygdala is required for the acquisition and expression of cue-conditioned fear responses using several kinds of antagonists. Little is known, however, about the signal transduction pathway and molecular substrate underlying fear conditioning. Here we use NMDA receptor-deficient mice to demonstrate that calmodulin-dependent kinase II, CaMKIIbeta, and CaMKIIalpha activation involves the NR2A subunit in the lateral/basolateral amygdala during memory retrieval following auditory fear conditioning. These results suggest that auditory fear conditioning involves a close linkage between NMDA2A receptors and the CaMKII cascade.
authors.affiliation: Department of Pharmacology, School of Human Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Moriya
authors.forename: Y
authors.initials: Y
authors.lastname: Kouzu
authors.forename: S
authors.initials: S
authors.lastname: Shibata
authors.forename: H
authors.initials: H
authors.lastname: Kadotani
authors.forename: K
authors.initials: K
authors.lastname: Fukunaga
authors.forename: E
authors.initials: E
authors.lastname: Miyamoto
authors.forename: T
authors.initials: T
authors.lastname: Yoshioka
mesh_terms: D000161:Acoustic Stimulation; D000679:Amygdala / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D001303:Auditory Cortex / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000502:physiology; D004597:Electroshock; D005239:Fear / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006358:Hot Temperature; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism*; D013216:Reflex, Startle / Q000502:physiology
chemical_list: C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517671:Camk2a protein, mouse; D002118:Calcium