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

Cerebellar long-term synaptic depression (LTD) is a model system of neurona l information storage that is expressed postsynaptically as a functional do wn-regulation of alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. What properties of postsynaptic AMPA receptors are change d? Several lines of evidence argue against changes in AMPA-receptor kinetic s. 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 desensitiza tion-reducing compound cyclothiazide. Finally, rapid application of glutama te to lifted PCs revealed no significant alterations in AMPA-receptor kinet ic properties after LTD induction. When this system was used to apply varyi ng concentrations of glutamate, no alteration in AMPA-receptor glutamate af finity was seen after LTD induction. Finally, peak-scaled nonstationary flu ctuation 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 L TD may be expressed solely as a reduction in the number of functional AMPA receptors in the postsynaptic density.