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TitleThe molecular infrastructure of glutamatergic synapses in the mammalian forebrain.
Journal, issue, pagesElife, Vol. 13, Year 2025
Publish dateSep 25, 2025
AuthorsJulia Peukes / Charlie Lovatt / Conny Leistner / Jerome Boulanger / Dustin R Morado / Martin J G Fuller / Wanda Kukulski / Fei Zhu / Noboru H Komiyama / John A G Briggs / Seth G N Grant / René A W Frank /
PubMed AbstractGlutamatergic 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. ...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.
External linksElife / PubMed:40996785 / PubMed Central
MethodsEM (tomography) / EM (subtomogram averaging)
Resolution25.0 Å
Structure data

EMDB-53528: Tomogram of a PSD95-containing glutamatergic synapse from 'ultra fresh' prepared mouse.
Method: EM (tomography)

EMDB-54246: Subtomogram average of an ionotropic glutamate receptor within mammalian glutamatergic synapses
Method: EM (subtomogram averaging) / Resolution: 25.0 Å

Source
  • Mus musculus (house mouse)

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