The expression of cerebellar LTD in culture is not associated with changes in AMPA-receptor kinetics, agonist affinity, or unitary conductance
Open Access
- 13 November 2001
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 98 (24) , 14066-14071
- https://doi.org/10.1073/pnas.241384598
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 α-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].Keywords
This publication has 29 references indexed in Scilit:
- Kinetic Model of Excitatory Synaptic Transmission to Cerebellar Purkinje CellsJournal of Theoretical Biology, 1997
- Dendritic and somatic glutamate receptor channels in rat cerebellar Purkinje cellsThe Journal of Physiology, 1997
- A Protein Synthesis–Dependent Late Phase of Cerebellar Long-Term DepressionNeuron, 1996
- Defining a Minimal Computational Unit for Cerebellar Long-Term DepressionNeuron, 1996
- Prolonged presence of glutamate during excitatory synaptic transmission to cerebellar Purkinje cellsNeuron, 1994
- Properties of glutamate receptors are modified during long-term depression in rat cerebellar Purkinje cellsNeuroscience Research, 1994
- Estimated conductance of glutamate receptor channels activated during EPSCs at the cerebellar mossy fiber-granule cell synapseNeuron, 1993
- Participation of Postsynaptic PKC in Cerebellar Long-Term Depression in CultureScience, 1991
- A long-term depression of AMPA currents in cultured cerebellar purkinje neuronsNeuron, 1991
- Activation of protein kinase C induces a long-term depression of glutamate sensitivity of cerebellar Purkinje cells. An in vitro studyBrain Research, 1988