The Significance Of Calcium / Calmodulin-Dependent SKA II?

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The significance of the enzyme Calcium/calmodulin-dependent kinase II (CaMKII) in synaptic long-term potentiation (LTP), and hence as a molecular underpin of memory, was demonstrated by Lisman et al., 1 but at the level of a single synapse, the localization of CaMKII nor its activity in the spine was previously known. Lee et al. 2 used the technique of fluorescence resonance energy transfer (FRET) and two-photon fluorescence lifetime imaging microscopy to visualize the dynamics of CaMKII in a single spine, including its role in synapse specificity, the degree of its compartmentalization, and its maintenance of LTP. The authors stimulated a single dendritic spine with zero extracellular Mg2+ in the presence of various pharmacological …show more content…

That did not answer, however, the behavior of Ca2+ and CaMKII in vivo, as NMDARs have a Mg2+ block that requires simultaneous postsynaptic depolarization and synaptic activation to be removed. 7 The authors proceeded to image CaMKII in a LTP induction protocol with both glutamate uncaging and postsynaptic depolarization with extracellular Mg2+. They performed whole-cell patch clamp recordings and measured the EPSC and spine volume to be increased for longer than 60 minutes. They observed that although [Ca2+] returned to baseline within 2 seconds, depolarization sustained for more than a minute, which increased CaMKII activity in dendritic shafts but not spines, where CaMKII activation required glutamate uncaging pulses. CaMKII, as they indicated, decayed within two minutes, which contradicted previous suggestions that it remains active for hours after activation by NMDA-mediated Ca2+ influx. 1,6 Taken together, these findings address the synapse specificity of LTP, as both Ca2+ and CaMKII decay too quickly to diffuse and influence other synapses. While the dynamics of CaMKII in LTP had thus far been elucidated, it still begged the question as to why postsynaptic depolarization alone could not induce LTP across the dendritic shaft. Since it was known that postsynaptic depolarization caused a large, sustained increase in Ca2+ in spines, 8 the authors

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