| First Author | Yamagata Y | Year | 2018 |
| Journal | eNeuro | Volume | 5 |
| Issue | 4 | PubMed ID | 30225347 |
| Mgi Jnum | J:266891 | Mgi Id | MGI:6256922 |
| Doi | 10.1523/ENEURO.0133-18.2018 | Citation | Yamagata Y, et al. (2018) Differential Involvement of Kinase Activity of Ca(2+)/Calmodulin-Dependent Protein Kinase IIalpha in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse. eNeuro 5(4):ENEURO.0133-18.2018 |
| abstractText | Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) is a key mediator of activity-dependent neuronal modifications and has been implicated in the molecular mechanisms of learning and memory. Indeed, several types of CaMKIIalpha knock-in (KI) and knock-out (KO) mice revealed impairments in hippocampal synaptic plasticity and behavioral learning. On the other hand, a similar role for CaMKIIalpha has been implicated in amygdala-dependent memory, but detailed analyses have not much been performed yet. To better understand its involvement in amygdala-dependent memory as compared to hippocampus-dependent memory, here we performed biochemical analyses and behavioral memory tests using the kinase-dead CaMKIIalpha (K42R)-KI mouse. In the Morris water maze tasks, homozygous mutants performed well in the visible platform trials, while they failed to form spatial memory in the hippocampus-dependent hidden platform trials. In fear conditioning, these mice were impaired but showed a certain level of amygdala-dependent cued fear memory, which lasted four weeks, while they showed virtually no hippocampus-dependent context discrimination. Neither stronger stimulation nor repetitive stimulation compensated for their memory deficits. The differential outcome of hippocampus- and amygdala-dependent memory in the mutant mouse was not due to differential expression of CaMKIIalpha between the hippocampus and the amygdala, because biochemical analyses revealed that both kinase activity and protein levels of CaMKII were indistinguishable between the two brain regions. These results indicate that kinase activity of CaMKIIalpha is indispensable for hippocampus-dependent memory, but not necessarily for amygdala-dependent memory. There may be a secondary, CaMKIIalpha activity-independent pathway, in addition to the CaMKIIalpha activity-dependent pathway, in the acquisition of amygdala-dependent memory. |
