Subsynaptic AMPA receptor distribution is acutely regulated by actin-driven reorganization of the postsynaptic density
dc.contributor.author | Kerr, Justin Matthew | |
dc.date.accessioned | 2012-06-29T15:34:54Z | |
dc.date.available | 2012-06-29T15:34:54Z | |
dc.date.issued | 2011 | |
dc.identifier.uri | http://hdl.handle.net/10713/1670 | |
dc.description | University of Maryland, Baltimore. Neuroscience. Ph.D. 2012 | en_US |
dc.description.abstract | AMPA receptors (AMPARs) mediate synaptic transmission and plasticity during learning, development, and disease. Mechanisms determining subsynaptic receptor position are poorly understood but are key determinants of synapse strength. I used a series of live-cell high-resolution imaging approaches to measure protein organization within single synapses in rat hippocampal neurons. By photobleaching receptors in synapse subdomains, I found that most AMPARs do not freely diffuse within the synapse, indicating they are embedded in a matrix that determines their subsynaptic position. However, time lapse analysis revealed that synaptic AMPARs are continuously repositioned by plasticity of this scaffold matrix and not by diffusion within the synapse. Using a fluorescence correlation analysis, I found that across the lateral extent of single PSDs, component proteins were differentially distributed, and this distribution was continually adjusted by actin treadmilling. The C-terminal PDZ ligand of GluA1 did not regulate its mobility or distribution in the synapse, but glutamate receptor activation promoted subsynaptic mobility. Strikingly, subsynaptic immobility of both AMPARs and scaffold molecules remained essentially intact even after loss of actin filaments. I conclude that receptors are actively repositioned at the synapse by treadmilling of the actin cytoskeleton, an influence which is transmitted only indirectly to receptors via the pliable and surprisingly dynamic internal structure of the PSD. | en_US |
dc.language.iso | en_US | en_US |
dc.subject.mesh | Actin Cytoskeleton | en_US |
dc.subject.mesh | Hippocampus | en_US |
dc.subject.mesh | Neurons | en_US |
dc.subject.mesh | Post-Synaptic Density | en_US |
dc.subject.mesh | Receptors, AMPA | en_US |
dc.subject.mesh | Synapses | en_US |
dc.title | Subsynaptic AMPA receptor distribution is acutely regulated by actin-driven reorganization of the postsynaptic density | en_US |
dc.type | dissertation | en_US |
dc.contributor.advisor | Blanpied, Thomas A. | |
dc.identifier.ispublished | No | |
refterms.dateFOA | 2019-02-19T16:28:52Z |