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

According to the synaptic tagging-and-capture hypothesis, long-lasting (late-phase) plasticity requires the synthesis of plasticity-related proteins and the setting of a synaptic tag at the stimulated synapse. It has been hypothesized that this tag is implemented by the complex interplay between dendritic spine geometry and the scaffolding protein actin.

To test this, we propose a biophysically-grounded model of late-phase synaptic plasticity considering dynamic and stable actin pools and the size of the PSD in the synapse. In our model, the tag corresponds to the imbalance between the spine volume determined by actin and the volume that would be expected for the current PSD size.

We demonstrate the viability of the proposed model by showing that it can account for the experimentally observed synaptic plasticity induced by stimulation of a single synapse, as well as tag-resetting protocols, and heterosynaptic plasticity protocols involving two synapses.

Moreover, for the interaction of two consecutive stimuli at the same synapse within around up to an hour, plastic changes stack non-linearly, reminiscent of the spacing effect found in learning and memory studies.

In summary, our model both matches experiments and extrapolates well to a wide range of stimulation protocols. Thus, it will be ideally suited to serve as a basis to predict the plasticity effects emerging from the complex activity patterns in recurrent networks.