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 (mGluR1) 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 PKCγ-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCβ4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCβ1 was expressed weakly and uniformly, PLCβ2 was not detected, PLCβ3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCβ4 was expressed uniformly throughout. In PLCβ4-deficient mice, expression of total PLCβ, the mGluR1-mediated Ca²⁺ response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCα, -βI, -βII, and -γ in mouse cerebellar Purkinje cells during LTD induction. Both PKCα and PKCβI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCβ4 in rostral cerebellar Purkinje cells induced LTD via PKCα and/or PKCβI.