Deletion of both alleles of the P/Q-type Ca2+-channel Cav2.1(α1A) subunit gene in mouse leads to severe ataxia and early death. Using cerebellar slices obtained from 10 to 15 postnatal days mice and cultured for at least 3 weeks in vitro, we have analysed the synaptic alterations produced by genetically ablating the P/Q-type Ca2+-channels, and compared them with the effect of pharmacological inhibition of the P/Q- or N-type channels on wild-type littermate mice. Analysis of spontaneous synaptic currents recorded in Purkinje cells (PCs) indicated that the P/Q-type channels play a prominent role at the inhibitory synapses afferent onto the PCs, with the effect of deleting Cav2.1(α1A) partially compensated. At the granule cell (GC) to PC synapses, both N- and P/Q-type Ca2+-channels were found playing a role in glutamate exocytosis, but with no significant phenotypic compensation of the Cav2.1(α1A) deletion. We also found that the P/Q- but not N-type Ca2+-channel is indispensable at the autaptic contacts between PCs. Tuning of the GC activity implicates both synaptic and sustained extrasynaptic γ-aminobutyric acid (GABA) release, only the former was greatly impaired in the absence of P/Q-type Ca2+-channels. Overall, our data demonstrate that both P/Q- and N-type Ca2+-channels play a role in glutamate release, while the P/Q-type is essential in GABA exocytosis in the cerebellum. Contrary to the other regions of the CNS, the effect of deleting the Cav2.1(α1A) subunit is partially or not compensated at the inhibitory synapses. This may explain why cerebellar ataxia is observed at the mice lacking functional P/Q-type channels.