Conditions for Synaptic Specificity during the Maintenance Phase of Synaptic Plasticity

Activity-dependent modifications of synaptic efficacies are a cellular substrate of learning and memory. Experimental evidence shows that these modifications are synapse specific and that the long-lasting effects are associated with the sustained increase in concentration of specific proteins like PKMζ. However, such proteins are likely to diffuse away from their initial synaptic location and spread out to neighboring synapses, potentially compromising synapse specificity. In this article, we address the issue of synapse specificity during memory maintenance. Assuming that the long-term maintenance of synaptic plasticity is accomplished by a molecular switch, we carry out analytical calculations and perform simulations using the reaction-diffusion package in NEURON to determine the limits of synapse specificity during maintenance. Moreover, we explore the effects of the diffusion and degradation rates of proteins and of the geometrical characteristics of dendritic spines on synapse specificity. We conclude that the necessary conditions for synaptic specificity during maintenance require that molecular switches reside in dendritic spines. The requirement for synaptic specificity when the molecular switch resides in spines still imposes strong limits on the diffusion and turnover of rates of maintenance molecules, as well as on the morphologic properties of synaptic spines. These constraints are quite general and apply to most existing models suggested for maintenance. The parameter values can be experimentally evaluated, and if they do not fit the appropriate predicted range, the validity of this class of maintenance models would be challenged.