Uncovering synaptic and cellular nanoarchitecture of brain tissue via seamless <i>in situ</i> trimming and milling for cryo-electron tomography.

ABSTRACT: Cell-cell communication underlies all emergent properties of the brain, including cognition, learning and memory. The physical basis for these communications is the synapse, a multi-component structure requiring coordinated interactions between diverse cell types. However, many aspects of three-dimensional (3D) synaptic organization remain poorly understood. Here, we developed an approach, seamless in situ trimming and milling (SISTM), to reliably fabricate sufficiently thin lamellae for mapping of the 3D nanoarchitecture of synapses in mouse, monkey and human brain tissue under near-native conditions via cryo-electron tomography (cryo-ET). We validated SISTM in a mouse model of Huntington's disease, demonstrating distinct 3D alterations to synaptic vesicles and mitochondria. By suc

SUBMITTER: Ning J 

PROVIDER: S-EPMC11952431 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature