The synaptic tag as an emergent biophysical state depending on the synaptic actin dynamics and the postsynaptic density

Abstract

According to the synaptic tagging-and-capture hypothesis, long-term synaptic plasticity requires synapses to establish a synaptic tag, enabling them to capture plasticity-related products synthesized elsewhere in the neuron. The biophysical processes, molecules or properties that implement the tag are, however, unclear. We hypothesize 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, we developed a computational model that integrates established calcium-dependent synaptic plasticity with the complex biochemical dynamics of the PSD and actin - a key structural protein determining dendritic spine geometry. This model can 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 repeated induction of plasticity within one hour results in a nonlinear accumulation of synaptic changes, reminiscent of the spacing effect observed in psychological studies of learning and memory. Hence, our model offers a concise mechanistic framework for understanding critical synaptic processes and demonstrates the viability of the hypothesis that temporal disparities in structural and biochemical dynamics form a memory trace that could act as a synaptic tag.