Mode of induction of long-term depression at parallel fibre--Purkinje cell synapses in rabbit cerebellar cortex.

In a superficial folium of the dorsal paraflocculus of high decerebrate rabbits, extracellular unitary spikes were recorded from a Purkinje cell, while two parallel fibre beams impinging onto that Purkinje cell were separately stimulated in the molecular layer. Climbing fibre afferents were stimulated at the contralateral inferior olive. Quisqualate was ionophoretically applied to the dendrite of the Purkinje cell intersecting one of the stimulated parallel fibre beams (test beam). Long-term depression (longer than 45 min) occurred in Purkinje cell responsiveness to the test beam, but not to the other beam (control beam), when quisqualate was applied for 4 min in conjunction with 2 Hz stimulation of climbing fibres. This effect was completely abolished by simultaneous application of a glutamate blocker, kynurenate, during conjunctive quisqualate-climbing fibre stimulation. Application of quisqualate alone caused a small degree of depression in parallel fibre-Purkinje cell transmission. This effect was abolished when spontaneous activity of climbing fibres was blocked by injection of tetrodotoxin or lidocaine to the contralateral inferior olive, and therefore was due to conjunction of quisqualate with spontaneous climbing fibre inputs that normally occurred at 0.5-1.2 Hz. These findings suggest that the occurrence of long-term depression is strictly dependent on conjunction of climbing fibre activity with quisqualate receptor activation.