Scheme of the cerebellar circuitry and the RNB technique. (a) The mossy fibers project directly to the interpositus nucleus and indirectly to Purkinje cells. The climbing fibers project to both Purkinje cells and the interpositus nucleus. Purkinje cells are the sole inhibitory output system from the cerebellar cortex. Feedback projections of several inhibitory interneurons are omitted in this diagram. Red X, blockade of granule cell transmission; yellow plus signs, excitatory; red minus signs, inhibitory. (b) In RNB mice, the expression of rtTA is confined to granule cells by the granule cell-specific GABAA receptor α6-subunit promoter. DOX-bound rtTA induces restrictedly the expression of tetanus toxin in granule cells, which in turn cleaves VAMP2 and blocks glutamatergic transmission. TRE, tetracycline-responsive element; CMV, cytomegalovirus promoter.