Synaptically-evoked calcium release from endoplasmic reticulum (ER) calcium stores is prominent in cerebellar Purkinje cells and is essential for cerebellar function. However, the mechanism by which the ER calcium content is maintained throughout many cycles of synaptic excitation is still a matter of debate for central neurons, including Purkinje cells. In non-excitable cells calcium stores are replenished through the action of stromal interaction molecule (STIM) and Orai proteins that have been shown to closely associate and interact with members of the canonical transient receptor potential (TRPC) cation channel family. We found that in acute cerebellar slices, caffeine-induced depletion of Purkinje cell somatic calcium stores is followed by store-operated calcium entry (SOCE) in the absence of synaptic input and action potential firing. Moreover, SOCE persists in the absence of either TRPC1 or TRPC3, the predominantly expressed TRPC subunits in Purkinje cells, in the respective transgenic knockout mice. In wild type mice, we performed a quantitative RT-PCR analysis of STIM1,2 and Orai1-3 expression. In contrast to other brain regions in which STIM2 is the main STIM isoform (Berna-Erro, A. et al., 2009. Sci Signal 2, ra67), we found that in the cerebellum STIM1 is more abundantly expressed than STIM2. In Purkinje cells, the expression level of STIM1 is even higher than that of the total cerebellum. Single-cell RT-PCR analysis of Purkinje cells also showed that Orai2 is more abundant in these cells than the other two Orai isoforms. On the protein level, the presence of STIM1 and Orai2 in Purkinje cells was demonstrated by means of immuncytochemistry. To analyze the functions of STIM1, we created a Purkinje cell-specific STIM1-deficient mouse line by employing the Cre/loxP gene targeting strategy. Our first results indicate a prominent role of STIM1 for glutamatergic synaptic transmission.