Phospholipase Cβ4 and protein kinase Cα and/or protein kinase CβI are involved in the induction of long term depression in cerebellar Purkinje cells

Activation of the type-1 metabotropic glutamate receptor (mG1uR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKC gamma -deficient mice, thus, in the present study, we examined cerebellar LTD in PLC beta4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLC beta1 was expressed weakly and uniformly, PLC beta2 was not detected, PLC beta3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLC beta4 was expressed uniformly throughout. In PLC beta4-deficient mice, expression of total PLC beta, the mGluR1-mediated Ca2+ response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKC alpha, -betaI, -beta II, and -gamma in mouse cerebellar Purkinje cells during LTD induction. Both PKC alpha and PKC betaI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mG1uR1-mediated activation of PLC beta4 in rostral cerebellar Purkinje cells induced LTD via PKC alpha and/or PKC betaI.