1. Asynchronous release sites align with NMDA receptors in mouse hippocampal synapses
- Author
-
Hanieh Falahati, Christine Prater, Raul Ramos, Sumana Raychaudhuri, Shuo Li, Shigeki Watanabe, Tomas M. Bartol, Grant F. Kusick, Jing Wang, Eric Hosy, Marisa M Brockmann, Sarah Syed, Stephen A. Lee, Johns Hopkins University (JHU), Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Yale University School of Medicine, Brandeis University, The Salk Institute for Biological Studies, Interdisciplinary Institute for Neuroscience (IINS), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)
- Subjects
Male ,0301 basic medicine ,Science ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Models, Neurological ,Primary Cell Culture ,Action Potentials ,Glutamic Acid ,General Physics and Astronomy ,AMPA receptor ,Hippocampal formation ,Hippocampus ,Receptors, N-Methyl-D-Aspartate ,Synaptic Transmission ,Article ,Exocytosis ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Spatio-Temporal Analysis ,0302 clinical medicine ,mental disorders ,Synaptic vesicle exocytosis ,Animals ,Computer Simulation ,Receptors, AMPA ,Active zone ,Neurotransmitter ,Cells, Cultured ,Neurons ,Multidisciplinary ,Chemistry ,musculoskeletal, neural, and ocular physiology ,Depolarization ,General Chemistry ,Microscopy, Electron ,030104 developmental biology ,nervous system ,Astrocytes ,Synapses ,Biophysics ,NMDA receptor ,Female ,biological phenomena, cell phenomena, and immunity ,030217 neurology & neurosurgery ,psychological phenomena and processes - Abstract
Neurotransmitter is released synchronously and asynchronously following an action potential. Our recent study indicates that the release sites of these two phases are segregated within an active zone, with asynchronous release sites enriched near the center in mouse hippocampal synapses. Here we demonstrate that synchronous and asynchronous release sites are aligned with AMPA receptor and NMDA receptor clusters, respectively. Computational simulations indicate that this spatial and temporal arrangement of release can lead to maximal membrane depolarization through AMPA receptors, alleviating the pore-blocking magnesium leading to greater activation of NMDA receptors. Together, these results suggest that release sites are likely organized to activate NMDA receptors efficiently., Action potentials induce synchronous and asynchronous release of neurotransmitters. Here, the authors show that the synchronous and asynchronous release sites are aligned with AMPARs and NMDARs, respectively, in mouse hippocampal synapses. This organization allows efficient activation of NMDARs.
- Published
- 2021
- Full Text
- View/download PDF