Synaptic Condensates: Liquid–Liquid Phase Separation of Pre- and Postsynaptic Scaffold Proteins in Synapse Development and Memory Formation

Dear Colleagues,

Synapse development and memory formation are fundamental processes of the central nervous system, relying on the precise organization of proteins at both pre- and postsynaptic sites. In recent years, liquid–liquid phase separation (LLPS) has emerged as a key biochemical mechanism driving the dynamic assembly of synaptic components. This process allows scaffold proteins to form membrane-less condensates, enabling the spatial and temporal coordination of molecular interactions essential for synapse development and plasticity.

At the postsynaptic density (PSD), proteins such as PSD-95, Homer, and Shank undergo LLPS to form highly organized signaling hubs, which are critical for receptor localization and synaptic strength. Similarly, presynaptic scaffold proteins, including RIM, Bassoon, and ELKS, utilize LLPS to structure active zones and regulate neurotransmitter release. These phase-separated compartments are sensitive to neuronal activity and may serve as molecular substrates for experience-dependent plasticity.

This Special Issue explores how LLPS contributes to the structural and functional maturation of synapses and discusses emerging evidence linking synaptic condensates to memory formation. Understanding the role of phase separation in neural circuits may provide new insights into the molecular basis of learning and uncover novel targets for neurological disorder intervention.

Dr. Norbert Bencsik
Dr. Michel Baudry
Guest Editors

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