Pairing of pre‐ and postsynaptic activities in cerebellar Purkinje cells induces long‐term changes in synaptic efficacy in vitro.

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Abstract
1. An in vitro slice preparation of rat cerebellar cortex was used to analyse long‐lasting modifications of synaptic transmission at parallel fibre (PF)‐Purkinje cell (PC) synapses. These use‐dependent changes were induced by pairing PF‐mediated EPSPs evoked at low frequency (1 Hz) with different levels of membrane polarization (or bioelectrical activities) of PCs for 15 min. 2. Experiments were performed on forty‐eight PCs recorded intracellularly in a conventional perfused chamber, and in fifty other cells maintained in a static chamber either in the presence (n = 21) or in the absence (n = 29) of 400 nM‐phorbol 12,13‐dibutyrate (PDBu). 3. In these three experimental conditions, PF‐mediated EPSPs were always measured on PCs maintained at a holding potential of ‐75 mV, and further hyperpolarized by constant hyperpolarizing pulses. This allowed us both to test the input resistance of PCs and to avoid their firing during PF‐mediated EPSPs. 4. In all cells retained for the present study, latencies of PF‐mediated EPSPs evoked at 0.2 Hz were stable during the pre‐pairing period, and the same was true for their amplitude and time course. 5. In the perfused chamber, pairing of PF‐mediated EPSPs with the same hyperpolarization of PCs as that used for measurements of synaptic responses had no effect on these EPSPs in 30% of PCs. It induced long‐term depression (LTD) and long‐term potentiation (LTP) in 23 and 47% of the tested cells respectively (n = 17). 6. In the perfused chamber, pairing of PF‐mediated EPSPs with moderate depolarization of PCs (n = 19) giving rise to a sustained firing of sodium spikes significantly favoured the appearance of LTP as compared to the previous pairing protocol. However, there were still 27 and 15% of cells which showed no modification and LTD respectively. 7. In contrast, pairing of PF‐mediated EPSPs with calcium (Ca2+) spikes evoked by strong depolarization of PCs (n = 12) led to LTD of synaptic transmission in nearly half of the tested cells, whereas LTP was now observed in less than 20% of them. 8. In the static chamber and in the absence of PDBu, LTD of PF‐mediated EPSPs was observed in most cells, whatever the pairing protocol with sodium or Ca2+ spikes. 9. This shift towards LTD was significantly reversed by PDBu in the pairing protocol using firing of sodium spikes, but not in the case of pairings with Ca2+ spikes.(ABSTRACT TRUNCATED AT 400 WORDS)