Conditions for synaptic specificity during the maintenance phase of synaptic plasticity

Abstract

1Activity-dependent modifications of synaptic efficacies are a cellular substrate of 2 learning and memory. Experimental evidence shows that these modifications are 3 synapse-specific and that the long-lasting effects are associated with the sustained 4 increase in concentration of specific proteins like PKMζ. However, such proteins are 5 likely to diffuse away from their initial synaptic location and spread out to neighbor-6 ing synapses, potentially compromising synapse-specificity. In this paper we address 7 the issue of synapse-specificity during memory maintenance. Assuming that the 8 long-term maintenance of synaptic plasticity is accomplished by a molecular switch 9 we perform simulations using the reaction-diffusion package in NEURON and analyt-10 ical calculations to determine the limits of synaptic-specificity during maintenance. 11Moreover, we explore the effects of the diffusion and degradation rates of proteins 12 and of the geometrical characteristics of dendritic spines on synapse specificty. We 13 conclude that the necessary conditions for synaptic specificity during maintenance 14 require that protein synthesis occurs in dendritic spines and that the activated den-15 dritic spines exhibit small neck diameters. 16Overwhelming experimental evidence indicates that activity-dependent modification 18 of synaptic efficacies is the cellular substrate of learning and memory (Morris et 19 al.