Involvement of inositol trisphosphate in cerebellar long-term depression.

We examined the role of increases in Ca2+ from different sources in the induction of long-term depression (LTD) of glutamate or AMPA responsiveness in cultured Purkinje neurones. Photolysis of caged Ca2+ or caged inositol 1,4,5-trisphosphate (InsP3) as well as depolarization was used to increase Ca2+ concentration. Heparin, contained in a patch pipette to block InsP3 binding to its receptor, prevented LTD induction by coupling of glutamate application and depolarization. Although pairing of depolarization and AMPA application did not induce LTD, photolysis of caged InsP3 in conjunction with depolarization and AMPA application induced LTD. The results suggest that not only Ca2+ influx through voltage-gated Ca channels but also InsP3-induced Ca2+ mobilization are involved in LTD induction.