Input-Specific Metaplasticity by a Local Switch in NMDA Receptors

dc.contributor.advisor

Ehlers, Michael D

dc.contributor.advisor

West, Anne E

dc.contributor.author

Lee, Ming-Chia

dc.date.accessioned

2009-05-01T18:30:47Z

dc.date.available

2011-07-26T04:30:04Z

dc.date.issued

2009

dc.department

Neurobiology

dc.description.abstract

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.

dc.identifier.uri

https://hdl.handle.net/10161/1148

dc.language.iso

en_US

dc.subject

Biology, Neuroscience

dc.subject

Input

dc.subject

specific

dc.subject

LTP

dc.subject

Metaplasticity

dc.subject

NMDA receptors

dc.subject

Plasticity threshold

dc.title

Input-Specific Metaplasticity by a Local Switch in NMDA Receptors

dc.type

Dissertation

duke.embargo.months

24

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
D_Lee_Ming-Chia_a_200904.pdf
Size:
2.83 MB
Format:
Adobe Portable Document Format

Collections