# Sonication dissociates the synaptic cleft and allows purification of postsynaptic densities with associated postsynaptic membrane

## TL;DR

This paper shows that sonication can separate synaptic compartments without chemicals, enabling better study of postsynaptic structures.

## Contribution

A novel method using sonication to isolate postsynaptic densities without chemical/enzymatic treatments.

## Key findings

- Sonication dissociates the synaptic cleft without chemical/enzymatic treatments.
- Postsynaptic densities (PSDs) can be purified with their associated membrane using this method.
- The method preserves glutamatergic receptors in a near-native state for further study.

## Abstract

In the synaptic junction, pre-and post compartments are anchored to each other through trans-synaptic bridges spanning the synaptic cleft. Here we demonstrate that mild mechanical disturbance through sonication dissociates the synaptic cleft, and releases PSDs adjoined to the postsynaptic membrane, but devoid of presynaptic elements. It is the first time, to our knowledge, that dissection of the synaptic cleft has been achieved without the use of chemical/enzymatic treatments. This observation suggests that some of the protein-protein interactions involved in the anchoring of pre- and postsynaptic compartments are relatively weak non-covalent associations. We describe a method for the further fractionation of PSDs with the associated postsynaptic membrane. This PSD preparation provides a valuable tool for studies of postsynaptic membrane components, such as glutamatergic receptors, in an environment closer to their native state.

The online version contains supplementary material available at 10.1186/s13041-025-01217-7.