Heterosynaptic Molecular Dynamics: Locally Induced Propagating Synaptic Accumulation of CaM Kinase II

Calcium-calmodulin-dependent protein kinase 11 (CaMKII) is a key mediator of synaptic plasticity and learning. Global pyramidal cell glutamate stimulation induces translocation of CaMKII from dendritic shafts to spines. Here we show that local dendritic stimulation by puffing glutamate onto a region containing 7-32 synapses induces translocation of CaMKII to synapses initially at the puff site but that translocation subsequently spreads within dendrites to the distal dendrite arbor, resulting in a persistent, widespread synaptic accumulation. This locally induced propagating synaptic (L-IPS) accumulation of CaMKII requires activation of NMDA receptors and L-type Ca2+ channels and is preceded by a Ca2+ spike. L-IPS translocation of CaMKII alters biochemical signaling and is associated with an increase in AMPA receptor GluR1 at both stimulated and nonstimulated synapses and thus provides a molecular mechanism for heterosynaptic plasticity.