Conditions for synaptic specificity during the maintenance phase of synaptic plasticity

Abstract

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 PKM{zeta}. 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 paper 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 perform simulations using the reaction-diffusion package in NEURON and analytical calculations to determine the limits of synaptic-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 specificty. We conclude that the necessary conditions for synaptic specificity during maintenance require that protein synthesis occurs in dendritic spines and that the activated dendritic spines exhibit small neck diameters.