Input-Specific Metaplasticity by a Local Switch in NMDA Receptors

Loading...

Date

2009

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

334
views
460
downloads

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.

Department

Description

Provenance

Subjects

Biology, Neuroscience, Input, specific, LTP, Metaplasticity, NMDA receptors, Plasticity threshold

Citation

Citation

Lee, Ming-Chia (2009). Input-Specific Metaplasticity by a Local Switch in NMDA Receptors. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/1148.

Collections


Except where otherwise noted, student scholarship that was shared on DukeSpace after 2009 is made available to the public under a Creative Commons Attribution / Non-commercial / No derivatives (CC-BY-NC-ND) license. All rights in student work shared on DukeSpace before 2009 remain with the author and/or their designee, whose permission may be required for reuse.