STIMULUS PARAMETERS FOR INDUCTION OF LONG-TERM DEPRESSION IN IN-VITRO RAT PURKINJE-CELLS

Long-term depression (LTD) was induced in rat cerebellar slices by conjunctive stimulation of parallel fibers (PFs) and climbing fibers (CFs) under perfusion of 20 mu M picrotoxin, LTD was estimated by the reduction in the initial rising slope of EPSPs PF-induced in Purkinje cell dendrites. LTD-inducing efficacy was represented by both the average amount of depression and the probability of inducing depression greater than 25%, both measured at 40 min after the onset of conjunctive stimulation. Using 300 regularly recurring pulses given to both CFs and PFs with 0 ms interval, LTD was optimally induced at 1 Hz, and to lesser degrees at other frequencies. When the number of conjunctive stimuli at 1 Hz with zero CF-PF interval was varied from 50 to 500, 300 stimuli induced LTD most robustly. When CF-PF interval was varied while 300 pulses were given at 0.25-4 Hz, LTD was induced even when PF stimuli were delayed after CF stimuli by as much as 2 s, but it was inhibited when PF stimuli preceded CF stimuli by 10-100 ms. LTD was also induced by applying repeated short pulse trains to both CFs and PFs, but repeated application of a PF stimulus train immediately followed by a CF stimulus train as in classical conditioning was effectless. The present results suggest complex processes leading to LTD as a result of conjunctive CF and PF stimulation.