Compatibility between itinerant synaptic receptors and stable postsynaptic structure

TL;DR

This paper presents a mesoscopic model explaining how synaptic receptor density remains stable through a balance of exchange and cooperative interactions, leading to the formation of distinct postsynaptic domains.

Contribution

It introduces a novel multi-layer, topological mesoscopic model that captures the regulation and stability of synaptic receptor densities.

Findings

Receptors and scaffold molecules exchange rapidly, yet their density remains stable.

The model predicts a phase change leading to well-defined postsynaptic domains.

Theoretical framework for understanding synaptic stability and receptor organization.

Abstract

The density of synaptic receptors in front of presynaptic release sites is stabilized in the presence of scaffold proteins, but the receptors and scaffold molecules have local exchanges with characteristic times shorter than that of the receptor-scaffold assembly. We propose a mesoscopic model to account for the regulation of the local density of receptors as quasiequilibrium. It is based on two zones (synaptic and extrasynaptic) and multi-layer (membrane, sub-membrane and cytoplasmic) topological organization. The model includes the balance of chemical potentials associated with the receptor and scaffold protein concentrations in the various compartments. The model shows highly cooperative behavior including a "phase change" resulting in the formation of well-defined post-synaptic domains. This study provides theoretical tools to approach the complex issue of synaptic stability at the synapse, where receptors are transiently trapped yet rapidly diffuse laterally on the plasma membrane.