Controlling the Formation of Multiple Condensates in the Synapse

The postsynaptic density (PSD) is a molecule rich structure that continuously adapts its organization controlling synaptic physiology and transmission. Experimental studies have shown that this organization is dominated by the formation of condensates or (nano)clusters and by the seamless transition in their numbers as response to synaptic plasticity. In this study, we utilize different computational modeling frameworks to show that variations in the level of local protein concentrations together with the modulation of protein binding strengths can be key molecular factors in controlling the formation and number of clusters in the synapse. Comparison to MINFLUX data of spatial localization of PSD95 in the postsynapse under different activity conditions allowed us to derive predictions about the correlation between these two factors across a population of synapses. Co-variations of the factors, to mimic a simple LTP protocol, shows that a PSD containing a single cluster can reorganize to form multiple clusters that persists for long periods of time, providing a potential explanation of recent experimental data of PSD reorganization.