Synaptic memory survives molecular turnover

Activation of Ca2+/calmodulin-dependent kinase II (CaMKII) plays a critical role in long-term potentiation (LTP), a long accepted cellular model for learning and memory. However, how LTP and memories survive the turnover of synaptic proteins, particularly CaMKII, remains a mystery. Here, we take advantage of the finding that constitutive Ca2+-independent CaMKII activity, acquired prior to slice preparation, provides a lasting memory trace at synapses. In slice culture, this persistent CaMKII activity, in the absence of Ca2+ stimulation, remains stable over a 2-wk period, well beyond the turnover of CaMKII protein. We propose that the nascent CaMKII protein present at 2 wk acquired its activity from preexisting active CaMKII molecules, which transferred their activity to newly synthesized CaMKII molecules and thus maintain the memory in the face of protein turnover.

Automated summary

Activation of Ca2+/calmodulin-dependent kinase II (CaMKII) plays a critical role in long-term potentiation (LTP), but how LTP and memories survive the turnover of synaptic proteins remains a mystery. In this study, it was found that constitutive Ca2+-independent CaMKII activity acquired before slice preparation provides a lasting memory trace at synapses, which remains stable over a 2-week period in slice culture.