AMPA receptors (AMPARs) are dynamically regulated at synapses, but the time course and location of their exocytosis and endocytosis are not known. Therefore, we have used ecliptic pHluorin-tagged glutamate receptor 2 to visualize changes in AMPAR surface expression in real time. We show that synaptic and extrasynaptic AMPARs respond very differently to NMDA receptor activation; there is a rapid internalization of extrasynaptic AMPARs that precedes the delayed removal of synaptic AMPARs.
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http://dx.doi.org/10.1523/JNEUROSCI.1042-04.2004 | DOI Listing |
bioRxiv
July 2024
Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign; Urbana, IL, 61801, USA.
Synaptic AMPA receptors (AMPARs) on neuronal plasma membranes are correlated with learning and memory. Using a unique labeling and super-resolution imaging, we have visualized the nanoscale synaptic and extra-synaptic organization of native AMPARs for the first time in mouse brain slices as a function of brain region and tauopathy. We find that the fraction of surface AMPARs organized in synaptic clusters is two-times smaller in the hippocampus compared to the motor and somatosensory cortex.
View Article and Find Full Text PDFNeuron
August 2023
Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany; Signaling Research Centers BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany. Electronic address:
Information processing and storage in the brain rely on AMPA-receptors (AMPARs) and their context-dependent dynamics in synapses and extra-synaptic sites. We found that distribution and dynamics of AMPARs in the plasma membrane are controlled by Noelins, a three-member family of conserved secreted proteins expressed throughout the brain in a cell-type-specific manner. Noelin tetramers tightly assemble with the extracellular domains of AMPARs and interconnect them in a network-like configuration with a variety of secreted and membrane-anchored proteins including Neurexin1, Neuritin1, and Seizure 6-like.
View Article and Find Full Text PDFNat Commun
May 2023
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Precise alignment of pre- and postsynaptic elements optimizes the activation of glutamate receptors at excitatory synapses. Nonetheless, glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. To uncover the extrasynaptic actions of glutamate, we localized AMPA receptors (AMPARs) mediating spillover transmission between climbing fibers and molecular layer interneurons in the cerebellar cortex.
View Article and Find Full Text PDFJ Physiol
August 2023
Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, California, USA.
Synaptic plasticity involves modification of both biochemical and structural components of neurons. Many studies have revealed that the change in the number density of the glutamatergic receptor AMPAR at the synapse is proportional to synaptic weight update; an increase in AMPAR corresponds to strengthening of synapses while a decrease in AMPAR density weakens synaptic connections. The dynamics of AMPAR are thought to be regulated by upstream signalling, primarily the calcium-CaMKII pathway, trafficking to and from the synapse, and influx from extrasynaptic sources.
View Article and Find Full Text PDFiScience
December 2022
Neuroscience Graduate Program, UT Southwestern Medical Center, Dallas, TX 75390, USA.
A growing body of human literature implicates KIBRA in memory and neurodevelopmental disorders. Memory and the cellular substrates supporting adaptive cognition change across development. Using an inducible KIBRA knockout mouse, we demonstrate that adult-onset deletion of KIBRA in forebrain neurons impairs long-term spatial memory and long-term potentiation (LTP).
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