Persistent Accumulation of Calcium/Calmodulin-Dependent Protein Kinase II in Dendritic Spines after Induction of NMDA Receptor-Dependent Chemical Long-Term Potentiation

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a leading candidate for a synaptic memory molecule because it is persistently activated after long-term potentiation (LTP) induction and because mutations that block this persistent activity prevent LTP and learning. Previous work showed tha...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of neuroscience 2004-10, Vol.24 (42), p.9324-9331
Main Authors: Otmakhov, Nikolai, Tao-Cheng, Jung-Hwa, Carpenter, Stephen, Asrican, Brent, Dosemeci, Ayse, Reese, Thomas S, Lisman, John
Format: Article
Language:English
Subjects:
Adenylyl Cyclases - metabolism
Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cellular/Molecular
Colforsin - pharmacology
Dendritic Spines - drug effects
Dendritic Spines - enzymology
In Vitro Techniques
Long-Term Potentiation - drug effects
Long-Term Potentiation - physiology
Phosphodiesterase Inhibitors - pharmacology
Protein Binding - drug effects
Protein Transport - physiology
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate - physiology
Recombinant Fusion Proteins - metabolism
Rolipram - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Calcium/calmodulin-dependent protein kinase II (CaMKII) is a leading candidate for a synaptic memory molecule because it is persistently activated after long-term potentiation (LTP) induction and because mutations that block this persistent activity prevent LTP and learning. Previous work showed that synaptic stimulation causes a rapidly reversible translocation of CaMKII to the synaptic region. We have now measured green fluorescent protein (GFP)-CaMKIIalpha translocation into synaptic spines during NMDA receptor-dependent chemical LTP (cLTP) and find that under these conditions, translocation is persistent. Using red fluorescent protein as a cell morphology marker, we found that there are two components of the persistent accumulation. cLTP produces a persistent increase in spine volume, and some of the increase in GFP-CaMKIIalpha is secondary to this volume change. In addition, cLTP results in a dramatic increase in the bound fraction of GFP-CaMKIIalpha in spines. To further study the bound pool, immunogold electron microscopy was used to measure CaMKIIalpha in the postsynaptic density (PSD), an important regulator of synaptic function. cLTP produced a persistent increase in the PSD-associated pool of CaMKIIalpha. These results are consistent with the hypothesis that CaMKIIalpha accumulation at synapses is a memory trace of past synaptic activity.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.2350-04.2004