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

• 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
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.2350-04.2004

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.