Mapping proteomic composition of excitatory postsynaptic sites in the cerebellar cortex

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Cerebellar cortex functions rely on precise molecular composition at synapses.
• Previous mapping of glutamate receptors is incomplete, lacking data on scaffolding proteins like Shank2, linked to autism spectrum disorders.

Purpose of the Study:

• To map the distribution of multiple glutamate receptors, scaffolding, and signaling proteins at single synapse resolution in the cerebellar cortex.
• To investigate synapse-selective targeting patterns and their functional implications.

Main Methods:

• Utilized an adapted Magnified Analysis of the Proteome (MAP) expansion microscopy technique.
• Performed high-resolution mapping of synaptic proteins at individual synapses within the cerebellar cortex.

Main Results:

• Observed distinct, synapse-selective distribution patterns for various proteins, including AMPA receptors, Shank1, and Shank2.
• Revealed input-selective targeting within Purkinje cells and differential targeting of NMDA receptors and SynGAP to synaptic vs. extrasynaptic sites in glomeruli.
• Identified NMDA receptors and SynGAP at adherens junctions, suggesting a role in glomeruli structural plasticity.

Conclusions:

• The study contributes to mapping the cerebellar 'synaptome' by detailing protein distributions at single synapse resolution.
• Findings provide insights into the molecular organization of cerebellar circuits and potential mechanisms underlying neurodevelopmental disorders.
• Glomeruli function as integrative signaling units, differentially activating synaptic and extrasynaptic receptor complexes.