Temporal specificity of long-term depression in parallel fiber--Purkinje synapses in rat cerebellar slice

The phenomenon of cerebellar long-term depression (LTD), a decrease of synaptic strength between the parallel fibers (PFs) and Purkinje cells after conjunctive activation of PFs and the climbing fibers (CFs), is implicated as a cellular mechanism for motor learning. We have characterized a field-potential recording technique in cerebellar slice and have used the technique to examine the temporal conditions for cerebellar LTD induction in an attempt to examine the relevance of LTD to associative conditioning. Interstimulus intervals (ISIs) between onsets of PF and CF activation and the number of paired stimuli (pairings) were examined. LTD has distinct temporal specificity that seems to be constrained by inhibitory interneurons and can be masked by excessive stimulation. When 100 paired stimuli were given to PFs and CFs, LTD was induced with an ISI of 250 msec (PF activation preceding CF activation). In contrast, a smaller forward (125 msec), simultaneous (0 msec), or backward (-250 msec) ISIs were not effective for inducing LTD. However, the blockade of GABAA receptor-mediated inhibition made it possible to induce LTD with 100 pairs of simultaneous stimulations. Furthermore, by increasing the number of pairings to 600, significant LTD was observed with all four interstimulus intervals. These results suggest that temporal conditions for LTD induction share some similarity to associative learning of discrete motor responses.