Sensitivity of Synaptic Plasticity to the Ca2+ Permeability of NMDA Channels: A Model of Long-Term Potentiation in Hippocampal Neurons

We have examined a model by Holmes and Levy (1990) of the induction of associative long-term potentiation (LTP) by a rise in the free Ca2+ concentration ([Ca2+1) after synaptic activation of dendritic spines. The previously reported amplification of the change in [Ca2+l caused by coactivation of several synapses was found to be quite sensitive to changes in the permeability of the N-methyl-D-aspartate (NMDA) receptor channels to Ca2+. Varying this parameter indicated that maximum amplification is obtained at values that are close to Ca2+ permeabilities reported in the literature. However, amplification failed if permeability is reduced by more than 50%. We also found that the maximum free [Ca2+l reached in an individual spine during synaptic coactivation of several spines depended on the location of that spine on the dendritic tree. Distal spines attained a higher [Ca2+l than proximal ones, with differences of up to 80%. The implications of this result for the uniformity of induction of associative LTP in spines in different regions of the dendrite are discussed.