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Neurochemical Research

, Volume 44, Issue 3, pp 539–548 | Cite as

AMPA-Type Glutamate Receptor Conductance Changes and Plasticity: Still a Lot of Noise

  • Tim BenkeEmail author
  • Stephen F. Traynelis
Original Paper
  • 382 Downloads

Abstract

Twenty years ago, we reported from the Collingridge Lab that a single-channel conductance increase through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type ionotropic glutamate receptors (AMPARs) could mediate one form of plasticity associated with long-term potentiation (LTP) in the hippocampus (Benke et al., Nature 395:793–797, 1998). Revealed through peak-scaled non-stationary fluctuation analysis (PS-NSFA, also known as noise analysis), this component of LTP could be exclusively mediated by direct increases in channel conductance or by increases in the number of high conductance synaptic AMPARs. Re-evaluation of our original data in the light of the molecular details regarding AMPARs, conductance changes and plasticity suggests that insertion of high-conductance GluA1 homomers can account for our initial findings. Any potential cost associated with manufacture or trafficking of new receptors could be mitigated if pre-existing synaptic AMPARs also undergo a modest conductance change. The literature suggests that the presence of high conductance AMPARs and/or GluA1 homomers confers an unstable synaptic state, suggesting state transitions. An experimental paradigm is proposed to differentiate these possibilities. Validation of this state diagram could provide insight into development, disease pathogenesis and treatment.

Keywords

LTP Glutamate AMPA receptor Conductance Phosphorylation Rectification 

Notes

Acknowledgements

The author appreciates the input provided by Drs. Dell’Acqua, Aoto, Bayer and Kennedy, their laboratories and Dr. Caballes and Ms. Castano in the Benke laboratory. Supported by NIH NS101288 and the Children’s Hospital Colorado Foundation (Ponzio Family Chair in Neurology Research) (Benke) and NIH NS036654 (Traynelis).

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Authors and Affiliations

  1. 1.Departments of Pediatrics, Pharmacology, Neurology and OtolaryngologyUniversity of Colorado, School of MedicineAuroraUSA
  2. 2.Department of PharmacologyEmory University School of MedicineAtlantaUSA

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