Abstract
Vertebrate organisms adapt to a continuously changing environment by regulating the strength of synaptic connections between brain cells. Excitatory synapses are believed to increase their strength by vesicular insertion of transmitter glutamate receptors into the postsynaptic plasma membrane. These vesicles, however, have never been demonstrated or characterized. For the first time, we show the presence of small vesicles in postsynaptic spines, often closely adjacent to the plasma membrane and PSD (postsynaptic density). We demonstrate that they harbor vesicle-associated membrane protein 2 (VAMP2/synaptobrevin-2) and glutamate receptor subunit 1 (GluA1). Disrupting VAMP2 by tetanus toxin treatment reduces the concentration of GluA1 in the postsynaptic plasma membrane. GluA1/VAMP2-containing vesicles, but not GluA2/VAMP2-vesicles, are concentrated in postsynaptic spines relative to dendrites. Our results indicate that small postsynaptic vesicles containing GluA1 are inserted directly into the spine plasma membrane through a VAMP2-dependent mechanism.
Highlights
Synapses are junctions between neurons where the flow of information in the brain can be modified [1]
In order to test the antibody at the electron microscopical level, we performed immunogold labeling of hippocampus from newborn VAMP2 knockout mice (Fig 1D4) and wild type mice (Fig 1D3), immersion fixed with the same fixative as the one used for the rat experiments
In spite of a vast amount of research on the trafficking of glutamate receptors, we still do not know the details of the molecular mechanisms for delivery of glutamate receptors to the postsynaptic plasma membrane
Summary
Synapses are junctions between neurons where the flow of information in the brain can be modified [1]. Glutamate receptors of the AMPA (α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) class are tetramers of different subunits (GluA1-4) [3]. Through changes in the postsynaptic plasma membrane concentration of the AMPA receptors, enables the organism to adapt to changes in the environment [4, 5]. The receptors, or their subunits, recycle between cytoplasmic and membrane pools [6]. This cycling may allow fast, regulated changes in synaptic AMPA receptor concentration, enabling changes in synaptic strength [7]. No previous investigations have directly demonstrated the presence of such receptor-containing postsynaptic vesicles
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