A biophysical model of synaptic tagging-and-capture based on actin dynamics

Abstract

According to the synaptic tagging-and-capture hypothesis, long-term synaptic plasticity requires postsynaptic sites to establish a synaptic tag, enabling them to capture plasticity-related products synthesized elsewhere in the neuron. Although electrophysiological studies have provided evidence for the existence of synaptic tags, it remains largely unresolved which biophysical processes or synaptic molecules or properties implement them. In this study, we examine the hypothesis that a mismatch between dendritic spine volume and the size of the postsynaptic density (PSD) inheres the essential characteristics of a synaptic tag. To test this hypothesis, we developed a computational model that integrates established principles of calcium-dependent synaptic plasticity with the complex biochemical dynamics of actin, which is a key structural protein determining dendritic spine geometry. Using this model, we demonstrate the plausibility of our hypothesis by showing that the model can reproduce and explain a broad range of experimental findings across diverse synaptic plasticity protocols at the level of individual synapses as well as heterosynaptic plasticity protocols involving two synapses. Furthermore, the model predicts that the repeated induction of plasticity within a one-hour time window results in a nonlinear accumulation of synaptic changes, reminiscent of the spacing effect observed in psychological studies of learning and memory. These results offer a concise mechanistic framework for understanding critical synaptic processes and suggest how temporal disparities in structural and biochemical dynamics can form a memory trace that could act as a synaptic tag.