RT Journal Article
SR Electronic
T1 The molecular infrastructure of glutamatergic synapses in the mammalian forebrain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.19.432002
DO 10.1101/2021.02.19.432002
A1 J. Peukes
A1 M. Lovatt
A1 C. Leistner
A1 J. Boulanger
A1 D. R. Morado
A1 W. Kukulski
A1 F. Zhu
A1 N. Komiyama
A1 J. A. G. Briggs
A1 S. G. N. Grant
A1 R. Frank
YR 2021
UL http://biorxiv.org/content/early/2021/02/19/2021.02.19.432002.abstract
AB 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 synapses in the adult forebrain. The native glutamatergic synapse lacked a PSD. Instead, a concentrated ‘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 the architectural basis for synaptic remodeling. Clusters of 4-60 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 within mammalian brain synapses.Competing Interest StatementThe authors have declared no competing interest.