TY - JOUR T1 - CaMKII “Autonomy” Is Required for Initiating But Not for Maintaining Neuronal Long-Term Information Storage JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8214 LP - 8220 DO - 10.1523/JNEUROSCI.1469-10.2010 VL - 30 IS - 24 AU - Isabelle Buard AU - Steven J. Coultrap AU - Ronald K. Freund AU - Yong-Seok Lee AU - Mark L. Dell'Acqua AU - Alcino J. Silva AU - K. Ulrich Bayer Y1 - 2010/06/16 UR - http://www.jneurosci.org/content/30/24/8214.abstract N2 - Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) “autonomy” (T286-autophosphorylation-induced Ca2+-independent activity) is required for long-term potentiation (LTP) and for learning and memory, as demonstrated by CaMKII T286A mutant mice. The >20-year-old hypothesis that CaMKII stimulation is required for LTP induction, while CaMKII autonomy is required for LTP maintenance was recently supported using the cell-penetrating fusion-peptide inhibitor antCN27. However, we demonstrate here that ant/penetratin fusion to CN27 compromised CaMKII-selectivity, by enhancing a previously unnoticed direct binding of CaM to ant/penetratin. In contrast to antCN27, the improved cell-penetrating inhibitor tatCN21 (5 μm) showed neither CaM binding nor inhibition of basal synaptic transmission. In vitro, tatCN21 inhibited stimulated and autonomous CaMKII activity with equal potency. In rat hippocampal slices, tatCN21 inhibited LTP induction, but not LTP maintenance. Correspondingly, tatCN21 also inhibited learning, but not memory storage or retrieval in a mouse in vivo model. Thus, CaMKII autonomy provides a short-term molecular memory that is important in the signal computation leading to memory formation, but is not required as long-term memory store. ER -