Phase separation dynamics of SynGAP & PSD-95 in post-synaptic densities

The intricate interplay between SynGAP, PSD-95, and AMPA receptors within the post-synaptic density underpins synaptic plasticity and signal transmission. This study investigates several models of the interactions of these proteins, beginning with a minimal model of the kinetics of the exchange of SynGAP and AMPA receptors in the post- synaptic density after induction of long-term potentiation (LTP). Subsequently, we model the phenomenon of liquid-liquid phase separation (LLPS) mediated by the association of SynGAP and PSD-95. Our model of phase separation utilizes a three-component Flory-Huggins theory type (SynGAP, PSD-95, and solvent), and assumes energetically favorable interactions between SynGAP and PSD-95, as well as PSD-95 with itself. The model reproduces the phenomena of phase-separation-mediated formation of the post- synaptic density. We stimulate the dispersal of SynGAP from the post-synaptic density that follows an induction of LTP, which is modeled by a change in the Flory-Huggins interaction parameter representing the decreased favorability of SynGAP and PSD-95 interactions.