Autophosphorylation of αCaMKII is not a general requirement for NMDA receptor-dependent LTP in the adult mouse

Autophosphorylation of alpha-Ca(2+)/calmodulin kinase II (alpha CaMKII) at Thr(286) is thought to be a general effector mechanism for sustaining transcription-independent long-term potentiation (LTP) at pathways where LTP is NMDA receptor-dependent. We have compared LTP at two such hippocampal pathways in mutant mice with a disabling point mutation at the Thr(286) autophosphorylation site. We find that autophosphorylation of alpha CaMKII is essential for induction of LTP at Schaffer commissural-CA1 synapses in vivo, but is not required for LTP that can be sustained over days at medial perforant path-granule cell synapses in awake mice. At these latter synapses LTP is supported by cyclic AMP-dependent signalling in the absence of alpha CaMKII signalling. Thus, the autophosphorylation of alpha CaMKII is not a general requirement for NMDA receptor-dependent LTP in the adult mouse.