Cerebellar Purkinje cells (PCs) are innervated by granule cells (GCs) whose axons ascend into the molecular layer where they bifurcate to form parallel fibres (PFs). These extend laterally for several millimetres in both directions. Transmission of information along PFs to PCs may be more limited than previously thought (Cohen & Yarom, 1998). Moreover, synapses made by ascending axon segments onto PCs have a greater presynaptic vesicle density than PF synapses, suggesting a greater synaptic weight (Gundappa-Sulur et al. 1999). We have therefore compared the transmission properties of synapses formed onto PCs by ascending segments of granule cell axons and PFs.

Coronal cerebellar slices (250 µm thick) were prepared from the brains of 14- to 21-day-old male Wistar rats decapitated under isofluorane anaesthesia (inhalation). Whole-cell recordings were made from Purkinje cell somata voltage clamped at -70 mV at room temperature in the presence of 20 µM picrotoxin. One stimulating pipette was placed in the GC layer, directly below the recorded PC to activate ascending axon synapses. A second pipette was placed in the ML, 100 µm laterally, to activate PF synapses. All results are presented as means ± S.E.M.

Pairs of stimuli (50 ms interval) were applied to each pathway alternately at 0.2 Hz. The level of paired pulse facilitation of ML response (1.94 ± 0.06) was significantly higher than GC responses (1.59 ± 0.08; Mann-Whitney U test, P < 0.05, n = 6). Variance-mean analysis (Clements & Silver, 2000) performed under four different experimental conditions of release probability revealed that synapses activated by GC layer stimulation displayed a higher quantal content than those activated by ML stimulation (GL, 10.4 pA; ML, 7.7 pA) and a greater release probability (GL, 0.39; ML, 0.26; at 2.5 mM Ca²⁺).

Analysis of responses to trains of up to seven stimuli (50 ms interval) in 1 mM Ca²⁺ and the presence and absence of the AMPA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]qunioxaline-7-sulfonamide (NBQX) was conducted. NBQX (75 nM) reduced GL and ML responses to 56 ± 6 and 50 ± 2 %, respectively, of control values. The derived quantal amplitudes fell to 54 ± 12 and 56 ± 8 % of baseline levels, indicating a proportionally similar effect on AMPA receptors at both pathways. These data reveal fundamental differences in transmission properties between synapses made onto PCs by different segments of the same GC axons.