The expression of cerebellar LTD in culture is not associated with changes in AMPA-receptor kinetics, agonist affinity, or unitary conductance

Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14066-71. doi: 10.1073/pnas.241384598. Epub 2001 Nov 13.

Abstract

Cerebellar long-term synaptic depression (LTD) is a model system of neuronal information storage that is expressed postsynaptically as a functional down-regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. What properties of postsynaptic AMPA receptors are changed? Several lines of evidence argue against changes in AMPA-receptor kinetics. Neither LTD evoked in cultured granule-cell Purkinje cell (PC) pairs nor an LTD-like phenomenon evoked by phorbol ester application was associated with alterations in evoked AMPA receptor-mediated excitatory post-synaptic current (EPSC) or mEPSC kinetics. LTD produced by pairing glutamate pulses with depolarization was not altered by prior application of the desensitization-reducing compound cyclothiazide. Finally, rapid application of glutamate to lifted PCs revealed no significant alterations in AMPA-receptor kinetic properties after LTD induction. When this system was used to apply varying concentrations of glutamate, no alteration in AMPA-receptor glutamate affinity was seen after LTD induction. Finally, peak-scaled nonstationary fluctuation analysis was applied to estimate AMPA-receptor unitary conductance before and after LTD induction in a cultured cell pair, and this analysis too revealed no significant change. These results suggest that cerebellar LTD may be expressed solely as a reduction in the number of functional AMPA receptors in the postsynaptic density [Wang, Y.-T. & Linden, D. J. (2000) Neuron 25, 635-664].

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Benzothiadiazines / pharmacology
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / metabolism*
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Mice
  • Phorbol Esters / pharmacology
  • Quinoxalines / pharmacology
  • Receptors, AMPA / agonists
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors

Substances

  • Benzothiadiazines
  • Excitatory Amino Acid Antagonists
  • Phorbol Esters
  • Quinoxalines
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • phorbol-12,13-diacetate
  • Glutamic Acid
  • 2-Amino-5-phosphonovalerate
  • cyclothiazide