Synaptic modification of parallel fibre-Purkinje cell transmission in in vitro guinea-pig cerebellar slices.

1. Synaptic transmission from parallel fibres to Purkinje cells and its modification by paired stimulation of parallel fibres and climbing fibres were studied in in vitro slices of the cerebellum obtained from guinea-pigs. 2. Intracellular recordings were made from Purkinje cells, mainly from dendrites in the middle third of the molecular layer, but also, in a few cases, from somata. Climbing fibres were activated by stimulation of the white matter, while parallel fibres were stimulated with an electrode placed near the pial surface of the molecular layer. 3. Stimulation of the white matter elicited antidromic spikes, all-or-none climbing fibre responses, disynaptic responses through mossy fibres and parallel fibres, and trisynaptic responses through inhibitory interneurones. Climbing fibre responses were often followed by a small plateau potential, usually less than 2-3 mV in amplitude and less than 100 ms in duration, followed by a slow hyperpolarization which reached its peak in several seconds. Inhibitory inputs to Purkinje cells were blocked with picrotoxin for the experiments described below. 4. Stimulation of the superficial molecular layer with currents less than 50 microA produced graded parallel fibre-mediated excitatory postsynaptic potentials (e.p.s.p.s) ranging from 4 to 8 mV in peak amplitude. 5. Conjunctive stimulation of climbing fibres and parallel fibres at 4 Hz for 25 s induced depression of parallel fibre-mediated e.p.s.p.s in Purkinje cells, both in the peak amplitudes and in the slopes. The depression was about 30% on average and lasted for more than 50 min. 6. No such depression occurred when the intensity of the white matter stimulation was set just subthreshold for the climbing fibre innervating the Purkinje cell under study. Instead, the parallel fibre-mediated e.p.s.p.s were moderately potentiated for a period ranging from 10 to 50 min. Repetitive stimulation of the climbing fibre alone did not affect parallel fibre-mediated e.p.s.p.s. 7. Immediately after the conjunctive stimulation or the repetitive stimulation of climbing fibres alone, a transient hyperpolarization which lasted for several minutes was seen. Its time course was similar to that of the hyperpolarization following a climbing fibre response. Except for this, there were no associated changes in the membrane potential, the input resistance, or the magnitudes of climbing fibre responses in any of the cases mentioned in 5 and 6 above.