PAIRING-SPECIFIC LONG-TERM DEPRESSION OF PURKINJE-CELL EXCITATORY POSTSYNAPTIC POTENTIALS RESULTS FROM A CLASSICAL-CONDITIONING PROCEDURE IN THE RABBIT CEREBELLAR SLICE

1. Using a rabbit cerebellar slice preparation, we simulated a classic al conditioning procedure by stimulating parallel fiber inputs to Purk inje cells with the use of a brief, high-frequency train of eight cons tant-current pulses 80 ms before climbing fiber inputs to the same Pur kinje cell were stimulated with the use of a brief, lower frequency tr ain of three constant-current pulses. In all experiments, we assessed the effects of stimulation by measuring the peak amplitude of Purkinje cell excitatory postsynaptic potentials (EPSPs) to single parallel fi ber test pulses. 2. Intradendritically recorded Purkinje cell EPSPs un derwent a long-term (>20 min) reduction in peak amplitude (30%) after paired stimulation of the parallel and climbing fibers but not after u npaired or parallel fiber alone stimulation. We call this phenomenon p airing-specific long-term depression (PSD). 3. Facilitation of the pea k amplitude of a second EPSP elicited by a parallel fiber train occurr ed both before and after paired stimulation, suggesting that the locus of depression was not presynaptic. Depression of the peak amplitude o f a depolarizing response to focal application of glutamate following pairings of parallel and climbing tiber stimulation added support to a suggested postsynaptic locus of the PSD effect. 4. The application of aniracetam potentiated EPSP peak amplitude by 40%, but these values r eturned to baseline as a result of pairings. With the removal of anira cetam from the bath 20 min after pairings, normal levels of pairing-sp ecific EPSP depression were observed, indicating that the effect did n ot result from direct desensitization of ha-amino-3-hydroxy-5-methyl-4 -isoxazole-proprionic acid (AMPA) receptors. 5. Incubation of slices i n the protein kinase inhibitor H-7 potentiated EPSP peak amplitudes sl ightly (9%), but peak amplitudes returned to baseline levels after pai rings. The net reduction in EPSP peak amplitude of < 10% after pairing s suggested that H-7 partially blocked PSD and that, in turn, PSD invo lved protein kinases. 6. The means of induction and the specificity of those means suggest that the phenomenology of PSD is fundamentally di fferent from that of long-term depression. PSD only occurs with pairin gs of trains of parallel fiber and climbing fiber stimulation; it occu rs without the need for bicuculline; and it can overcome the blocking effects of aniracetam. 7. Nevertheless, the involvement of protein kin ases and the potential role of calcium suggest that the mechanisms inv olved in the induction of PSD and long-term depression have a number o f features in common. 8. Because of the pairing-specific nature of the long-term synaptic depression observed in these experiments, PSD prov ides a mechanism that may contribute to the role of the cerebellar cor tex in classical conditioning.