Fig. 3.

Adaptive timing of conditioned Purkinje cell responses. One of the most important common characteristics for both the conditioned eyeblink response and the conditioned Purkinje cell response is that the temporal response profile is adaptively timed in accordance with the CS-US interval (or interstimulus interval, ISI) indicated with blue, between presentation of the conditional stimulus (CS) and the unconditional stimulus (US). Just like conditioned eyeblink responses, conditioned Purkinje cell responses occur just prior to the expected onset of the unconditional stimulus. Panels (a–d) illustrate responses in four Purkinje cells that were conditioned using paired mossy fibre stimulation as the conditional stimulus (CS) and climbing fibre stimulation as the unconditional stimulus, separated by different CS-US intervals (interstimulus intervals, ISIs) indicated in blue—150, 200, 300 and 500 ms. The temporal profiles of the conditioned responses differ with regard to latencies to onset, maximum and offset in accordance with the interstimulus interval used during training. Longer interstimulus intervals compared to shorter caused acquisition of responses that had longer latencies to onset, maximum and offset. For each Purkinje cell, simple spike activity was recorded during 40 presentations of the conditional stimulus alone. The 40 records of 1,500 ms duration were aligned, with a 500-ms pre-stimulus period showing the Purkinje cell’s baseline simple spike activity, followed by the responses to presentations of the conditional stimulus. In the raster plots above the histograms, each dot represents the occurrence of a simple spike. Each bin in the histograms represents the average instantaneous simple spike frequency in a 10-ms time bin. Conditional stimulus durations varied between 300 and 800 ms but were always equal to or greater than the interstimulus interval. e Interstimulus intervals less than 100 ms are not conducive to conditioning of eyeblink responses. The same is true for the conditioned Purkinje cell response. Responses recorded from a Purkinje cell after conditioning to a 50-ms interstimulus interval between presentation of a 300-ms conditional stimulus, consisting of 31 electrical pulses delivered to the mossy fibres at 50 Hz, paired with electrical stimulation of the climbing fibres as the unconditional stimulus. In contrast to results after conditioning to interstimulus intervals of 150 ms or more (c–f below), training with a 50-ms interval does not produce a conditioned pause response but instead induces a learned excitatory response to the conditional stimulus. f The effects of CS-US intervals (or interstimulus interval, ISI) on conditioning of the rabbit behaviour (nictitating membrane response) are mirrored by the magnitude of conditioned Purkinje cell responses in ferrets. To compare the interstimulus interval effects on Purkinje cell responses and nictitating membrane responses, we re-plotted rabbit classical conditioning data on a reversed y-axis, as well as the mean Purkinje cell simple spike modulation as a function of interstimulus interval. (The curve showing Purkinje cell responses is shifted 5 ms backward to compensate for the shorter latency of climbing fibre activation that occurs with direct climbing fibre stimulation as the unconditional stimulus.) As can be seen, interstimulus intervals below 100 ms do not produce conditioning of either the behavioural response in the rabbit or the Purkinje cell pause response in the ferret. In fact, there is a strong match between the behavioural response frequency and the effect on Purkinje cell simple spike activity in response to the conditional stimulus, throughout the spectrum of interstimulus intervals from 0 to 300 ms. Adapted from [50, 57]