ArticleeLife2025
The molecular infrastructure of glutamatergic synapses in the mammalian forebrain.
Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- An unsuspected physiological role for mGluRIII glutamate receptors in hippocampal area CA1.Cell reports · 2026Article
- Memory engram synapse 3D macromolecular architecture visualized by cryoCLEM-guided cryoET.Structure (London, England : 1993) · 2026Article
- A generalizable and targeted molecular biopsy approach for in situ cryogenic electron tomography of vitreous brain tissue.Cell reports methods · 2025Article
- Memory engram synapse 3D molecular architecture visualized by cryoCLEM-guided cryoET.bioRxiv : the preprint server for biology · 2025Article
- 3D Super-Resolution Imaging of PSD95 Reveals an Abundance of Diffuse Protein Supercomplexes in the Mouse Brain.ACS chemical neuroscience · 2025Article
- Artificial intelligence insight on structural basis and small molecule binding niches of NMDA receptor.Computational and structural biotechnology journal · 2025Article
- The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain.Nature communications · 2023Article
- Bridging length scales from molecules to the whole organism by cryoCLEM and cryoET.Faraday discussions · 2022Article
- Label-free visual proteomics: Coupling MS- and EM-based approaches in structural biology.Molecular cell · 2022Review
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Authors and funding
12 authors.
Funding
Abstract
Glutamatergic synapses form the vast majority of connections within neuronal circuits, but how these subcellular structures are molecularly organized within the mammalian brain is poorly understood. Conventional electron microscopy using chemically fixed, metal-stained tissue has identified a proteinaceous, membrane-associated thickening called the 'postsynaptic density' (PSD). Here, we combined mouse genetics and cryo-electron tomography to determine the 3D molecular architecture of fresh isolated and anatomically intact synapses in the adult forebrain. The native glutamatergic synapse did not consistently show a higher density of proteins at the postsynaptic membrane, thought to be characteristic of the PSD. Instead, a 'synaptoplasm' consisting of cytoskeletal elements, macromolecular complexes, and membrane-bound organelles extended throughout the pre- and post-synaptic compartments. Snapshots of active processes gave insights into membrane remodeling processes. Clusters of up to 60 ionotropic glutamate receptors were positioned inside and outside the synaptic cleft. Together, these information-rich tomographic maps present a detailed molecular framework for the coordinated activity of synapses in the adult mammalian brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.