An evaluation of the synapse specificity of long‐term depression induced in rat cerebellar slices

Abstract

Whole-cell excitatory postsynaptic currents (EPSCs) were recorded from single Purkinje cells (PCs) in rat cerebellar slices in response to alternate activation of two separate sets of parallel fibres (PF1 and PF2). Pairing the stimulation of one input (PF1) with PC depolarisation at 1 Hz for 5 min produced varied effects, including a long-term depression (LTD) of subsequent responses, a medium-term potentiation, or no change relative to baseline levels (n = 14). In all but two cases PF2 responses mirrored those in PF1, in both direction and magnitude even though this second pathway was not specifically activated during pairing. Increasing the stimulus strength to evoke larger amplitude EPSCs (> 1000 pA) dramatically increased the proportion of cells that underwent LTD in both PF1 and PF2. LTD in both pathways was postsynaptic calcium dependent. PC depolarisation alone (n = 7) or PF1 stimulation paired with PC hyperpolarisation (n = 6) failed to induce LTD at either site. Pairing PF1 stimulation with climbing fibre (CF) activation at 1 Hz for 5 min produced LTD in the majority of cells regardless of the strength of PF stimulation. LTD under these conditions was not, however, input specific, even at the lowest stimulus strengths. With EPSCs greater than 1000 pA in amplitude, depression was apparent in both pathways even when the duration of PF1 pairing with depolarisation was limited to 1 min. Full expression of LTD in PF2 required stimulation of this pathway to be resumed within a distinct temporal window of conjunctive pairing with PF1. Introducing a delay of 20 min before resumption of PF2 activation preserved the input specificity of synaptic depression. We conclude that pairing either PC depolarisation or CF activation with stimulation of a discrete set of PFs produces LTD that spreads to adjacent synapses on the same PC.