STRONG ACTIVATION OF PARALLEL FIBERS PRODUCES LOCALIZED CALCIUM TRANSIENTS AND A FORM OF LTD THAT SPREADS TO DISTANT SYNAPSES

The temporal and spatial changes in intracellular calcium levels durin g separate activation of parallel fiber (PF) and climbing fiber (CF) i nputs to cerebellar Purkinje cells were studied. PF stimulation (1 Hz) , at relatively high stimulus strengths, led to accumulations of calci um that were similar in peak levels to those following CF stimulation but that remained spatially localized. Such stimuli consistently induc ed a durable depression of PF synaptic transmission that partially occ luded further depression by conventional conjunctive stimuli and that was independent of nitric oxide. This depression was accompanied by a reduction of synaptic efficacy in spatially isolated PF inputs to the same cell that was independent of postsynaptic calcium but that was me diated by nitric oxide. These data indicate that LTD comprises at leas t two separate processes and that parameters of PF stimulation that ar e capable of raising calcium levels in Purkinje cell dendrites are als o able to induce long-term changes in synaptic efficacy.