RT Journal Article SR Electronic T1 Conditions for Synaptic Specificity during the Maintenance Phase of Synaptic Plasticity JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0064-22.2022 DO 10.1523/ENEURO.0064-22.2022 VO 9 IS 3 A1 Marco A. Huertas A1 Adam J. H. Newton A1 Robert A. McDougal A1 Todd Charlton Sacktor A1 Harel Z. Shouval YR 2022 UL http://www.eneuro.org/content/9/3/ENEURO.0064-22.2022.abstract AB 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 PKMĪ¶. 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.