Show simple item record

dc.contributor.advisor Ehlers, Michael D en_US
dc.contributor.advisor West, Anne E en_US
dc.contributor.author Lee, Ming-Chia en_US
dc.date.accessioned 2009-05-01T18:30:47Z
dc.date.available 2011-07-26T04:30:04Z
dc.date.issued 2009 en_US
dc.identifier.uri http://hdl.handle.net/10161/1148
dc.description Dissertation en_US
dc.description.abstract <p>At excitatory synapses, NMDAR-mediated synaptic plasticity occurs in response to activity inputs by modifying synaptic strength. While comprehensive studies have been focused on the induction and expression mechanisms underlying synaptic plasticity, it is less clear whether and how synaptic plasticity itself can be subjected to regulations. The presence of "plasticity of plasticity", or meta-plasticity, has been proposed as an essential mechanism to ensure a proper working range of plasticity, which may also offer an additional layer of information storage capacity. However, it remains elusive whether and how meta-plasticity occurs at single synapses and what molecular substrates are locally utilized. Here, I develop systems allowing for sustained alterations of individual synaptic inputs. By implementing a history of inactivity at single synapses, I demonstrate that individual synaptic inputs control synaptic molecular composition homosynaptically, while allowing heterosynaptic integration along dendrites. Furthermore, I report that subunit-specific regulation of NMDARs at single synapses mediates a novel form of input-specific metaplasticity. Prolonged suppression of synaptic releases at single synapses enhances synaptic NMDAR-mediated currents and increases the number of functional NMDARs containing NR2B. Interestingly, synaptic NMDAR composition is adjusted by spontaneous glutamate release rather than evoked activity. I also demonstrate that inactivated synapses with more NMDARs containing NR2B acquire a lower induction threshold for long-term synaptic potentiation. Together, these results suggest that at single synapses, spontaneous release primes the synapse by modifying its synaptic state with specific molecular compositions, which in turn determine the synaptic gain in an input-specific manner.</p> en_US
dc.format.extent 2972379 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Biology, Neuroscience en_US
dc.subject Input en_US
dc.subject specific en_US
dc.subject LTP en_US
dc.subject Metaplasticity en_US
dc.subject NMDA receptors en_US
dc.subject Plasticity threshold en_US
dc.title Input-Specific Metaplasticity by a Local Switch in NMDA Receptors en_US
dc.type Dissertation en_US
dc.department Neurobiology en_US
duke.embargo.months 24 en_US

Files in this item

This item appears in the following Collection(s)

Show simple item record