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ERIC Number: EJ818786
Record Type: Journal
Publication Date: 2008-Nov
Pages: 7
Abstractor: As Provided
Reference Count: 0
ISBN: N/A
ISSN: ISSN-1072-0502
Autophosphorylation of [alpha]CaMKII is Differentially Involved in New Learning and Unlearning Mechanisms of Memory Extinction
Kimura, Ryoichi; Silva, Alcino J.; Ohno, Masuo
Learning & Memory, v15 n11 p837-843 Nov 2008
Accumulating evidence indicates the key role of [alpha]-calcium/calmodulin-dependent protein kinase II ([alpha]CaMKII) in synaptic plasticity and learning, but it remains unclear how this kinase participates in the processing of memory extinction. Here, we investigated the mechanism by which [alpha]CaMKII may mediate extinction by using heterozygous knock-in mice with a targeted T286A mutation that prevents the autophosphorylation of this kinase ([alpha]CaMKII[superscript T286A+/-]). Remarkably, partial reduction of [alpha]CaMKII function due to the T286A+/- mutation prevented the development of extinction without interfering with initial hippocampus-dependent memory formation as assessed by contextual fear conditioning and the Morris water maze. It is hypothesized that the mechanism of extinction may differ depending on the interval at which extinction training is started, being more akin to "new learning" at longer intervals and "unlearning" or "erasure" at shorter intervals. Consistent with this hypothesis, we found that extinction conducted 24 h, but not 15 min, after contextual fear training showed spontaneous recovery (reappearance of extinguished freezing responses) 21 d following the extinction, representing behavioral evidence for new learning and unlearning mechanisms underlying extinction 24 h and 15 min post-training, respectively. Importantly, the [alpha]CaMKII[superscript T286A+/-] mutation blocked new learning of contextual fear memory extinction, whereas it did not interfere with unlearning processes. Our results demonstrate a genetic dissociation of new learning and unlearning mechanisms of extinction, and suggest that [alpha]CaMKII is responsible for extinguishing memories specifically through new learning mechanisms.
Cold Spring Harbor Laboratory Press. 500 Sunnyside Boulevard, Woodbury, NY 11797-2924. Tel: 800-843-4388; Tel: 516-367-8800; Fax: 516-422-4097; e-mail: cshpres@cshl.edu; Web site: http://www.learnmem.org/
Publication Type: Journal Articles; Reports - Research
Education Level: N/A
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A