Show simple item record

dc.contributor.author Santamaria, F
dc.contributor.author Gonzalez, J
dc.contributor.author Augustine, GJ
dc.contributor.author Raghavachari, S
dc.date.accessioned 2011-06-21T17:31:12Z
dc.date.issued 2010
dc.identifier.citation PLoS computational biology, 2010, 6 (5), pp. e1000780 - ?
dc.identifier.issn 1553-7358
dc.identifier.uri http://hdl.handle.net/10161/4451
dc.description.abstract One mechanism of information storage in neurons is believed to be determined by the strength of synaptic contacts. The strength of an excitatory synapse is partially due to the concentration of a particular type of ionotropic glutamate receptor (AMPAR) in the post-synaptic density (PSD). AMPAR concentration in the PSD has to be plastic, to allow the storage of new memories; but it also has to be stable to preserve important information. Although much is known about the molecular identity of synapses, the biophysical mechanisms by which AMPAR can enter, leave and remain in the synapse are unclear. We used Monte Carlo simulations to determine the influence of PSD structure and activity in maintaining homeostatic concentrations of AMPARs in the synapse. We found that, the high concentration and excluded volume caused by PSD molecules result in molecular crowding. Diffusion of AMPAR in the PSD under such conditions is anomalous. Anomalous diffusion of AMPAR results in retention of these receptors inside the PSD for periods ranging from minutes to several hours in the absence of strong binding of receptors to PSD molecules. Trapping of receptors in the PSD by crowding effects was very sensitive to the concentration of PSD molecules, showing a switch-like behavior for retention of receptors. Non-covalent binding of AMPAR to anchored PSD molecules allowed the synapse to become well-mixed, resulting in normal diffusion of AMPAR. Binding also allowed the exchange of receptors in and out of the PSD. We propose that molecular crowding is an important biophysical mechanism to maintain homeostatic synaptic concentrations of AMPARs in the PSD without the need of energetically expensive biochemical reactions. In this context, binding of AMPAR with PSD molecules could collaborate with crowding to maintain synaptic homeostasis but could also allow synaptic plasticity by increasing the exchange of these receptors with the surrounding extra-synaptic membrane.
dc.format.extent e1000780 - ?
dc.language.iso en_US en_US
dc.relation.ispartof PLoS computational biology
dc.relation.isversionof 10.1371/journal.pcbi.1000780
dc.title Quantifying the effects of elastic collisions and non-covalent binding on glutamate receptor trafficking in the post-synaptic density.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-5-0 en_US
duke.description.endpage e1000780 en_US
duke.description.issue 5 en_US
duke.description.startpage e1000780 en_US
duke.description.volume 6 en_US
dc.relation.journal Plos Computational Biology en_US
pubs.issue 5
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Neurobiology
pubs.volume 6

Files in this item

This item appears in the following Collection(s)

Show simple item record