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.
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.
Moriya
T
T
Department of Pharmacology, School of Human Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
Kouzu
Y
Y
Shibata
S
S
Kadotani
H
H
Fukunaga
K
K
Miyamoto
E
E
Yoshioka
T
T
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
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