Ultrastructural membrane dynamics of mouse and human cortical synapses
Year: 2025
Type: article
Abstract: Live human brain tissues provide unique opportunities for understanding synaptic transmission. Investigations have been limited to anatomy, electrophysiology, and protein localization, while crucial parameters, such as synaptic vesicle dynamics, were not visualized. Here, we utilize zap-and-freeze time-resolved electron microscopy to overcome this hurdle. First, we validate the approach with calcium imaging in acute mouse brain slices. Next, we show that synaptic vesicle endocytosis is induced in both mouse and human brain slices. Crucially, clathrin-free pits appear immediately next to the active zone, where ultrafast endocytosis normally occurs, and can be trapped at this location by a dynamin inhibitor. In both species, a protein essential for ultrafast endocytosis, dynamin 1xA, localizes to the region peripheral to the active zone, the putative endocytic zone, indicating a possible conserved mechanism between mouse and human. This approach has the potential to reveal dynamic, high-resolution information about synaptic membrane trafficking in intact human brain slices.
Source: Neuron
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Howard Hughes Medical Institute, McKnight Endowment Fund for Neuroscience, Alfred P. Sloan Foundation, Brain Research Foundation, Simons Foundation, Esther A. and Joseph Klingenstein Fund, McKnight Foundation, Marine Biological Laboratory, Vallee Foundation, Johns Hopkins University, Diana Helis Henry Medical Research Foundation, Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, American Lebanese Syrian Associated Charities, Chan Zuckerberg Initiative, Universität Leipzig, Roland Ernst Stiftung, National Institutes of Health, Medizinische Fakultät, Universität Leipzig, National Institute on Aging, National Institute of Neurological Disorders and Stroke
Awards: PROGRAM TO DEVELOP RESEARCH IN IMMUNOLOGY OF AGING, G1619461779, G4133495015, G4173789599, G4188956608, G6327430379, G7100921548, G7114999742, Spatial and molecular determinants of fusion probability and timing, G7298191181, G7787298784, Request for Leica High-pressure Freezer and Automated Freeze-substitution System, Reviving electron microscopy for synaptic cell biology, G9000042841, G9000123503, Cognition & Hippocampal/Cortical Systems in Aging, NPTX2: Preserving memory circuits in normative aging and Alzheimer's Disease, Johns Hopkins Alzheimer's Disease Research Center
OpenAlex ID: W4416738639