In recent years much has been learned about the molecular requirements for inducing long-term synaptic depression (LTD) in various brain regions. However, very little is known about the consequences of LTD induction for subsequent signaling events in postsynaptic neurons. We have addressed this issue by examining homosynaptic LTD at the cerebellar climbing fiber (CF)-Purkinje cell (PC) synapse. This synapse is built for reliable and massive excitation: Activation of a single axon produces an unusually large alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated synaptic current, the depolarization of which drives a regenerative complex spike producing a large, widespread Ca(2+) transient in PC dendrites. Here we test whether CF LTD has an impact on dendritic, complex spike-evoked Ca(2+) signals by simultaneously performing long-term recordings of complex spikes and microfluorimetric Ca(2+) measurements in PC dendrites in rat cerebellar slices. Our data show that LTD of the CF excitatory postsynaptic current produces a reduction in both slow components of the complex spike waveform and complex spike-evoked dendritic Ca(2+) transients. This LTD of dendritic Ca(2+) signals may provide a neuroprotective mechanism and/or constitute "heterosynaptic metaplasticity" by reducing the probability for subsequent induction of those forms of use-dependent plasticity, which require CF-evoked Ca(2+) signals such as parallel fiber-PC LTD and interneuron-PC LTP.

Animals, Calcium Channels/drug effects/*physiology, Calcium/*metabolism, Cerebellar Cortex/physiology, Dendrites/*physiology, Dose-Response Relationship, Drug, Electrophysiology, Enzyme Inhibitors/pharmacology, Patch-Clamp Techniques, Phenanthridines/pharmacology, Purkinje Cells/*physiology, Rats, Rats, Sprague-Dawley, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Synapses/*physiology, Synaptic Transmission, Time Factors
dx.doi.org/10.1073/pnas.0536420100, hdl.handle.net/1765/13128
Proceedings of the National Academy of Sciences of the United States of America
Erasmus MC: University Medical Center Rotterdam

Weber, J.T, de Zeeuw, C.I, Hansel, C.R.W, & Linden, D.J. (2003). Long-term depression of climbing fiber-evoked calcium transients in Purkinje cell dendrites. Proceedings of the National Academy of Sciences of the United States of America, 100(5), 2878–2883. doi:10.1073/pnas.0536420100