Type 1 inositol 1,4,5-trisphosphate receptor is required for induction of long-term depression in cerebellar Purkinje neurons

The inositol 1,4,5-trisphosphate receptor (InsP3R) is an intracellular Ca²⁺ channel that releases Ca²⁺ from internal Ca²⁺ stores in response to InsP3. Although InsP3R is highly expressed in various regions of the mammalian brain, the functional role of this receptor has not been clarified. We show here that cerebellar slices prepared from mice with a disrupted InsP3R type 1 gene, which is predominantly expressed in Purkinje cells, completely lack long-term depression (LTD), a model of synaptic plasticity in the cerebellum. Moreover, a specific antibody against InsP3R1, introduced into wild-type Purkinje cells through patch pipettes, blocked the induction of LTD. These data indicate that, in addition to Ca²⁺ influx through Ca²⁺ channels on the plasma membrane, Ca²⁺ release from InsP3R plays an essential role in the induction of LTD, suggesting a physiological importance for InsP3R in Purkinje cells.