Abstract
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 PKCgamma-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCbeta4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCbeta1 was expressed weakly and uniformly, PLCbeta2 was not detected, PLCbeta3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCbeta4 was expressed uniformly throughout. In PLCbeta4-deficient mice, expression of total PLCbeta, the mGluR1-mediated Ca(2+) response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCalpha, -betaI, -betaII, and -gamma in mouse cerebellar Purkinje cells during LTD induction. Both PKCalpha and PKCbetaI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCbeta4 in rostral cerebellar Purkinje cells induced LTD via PKCalpha and/or PKCbetaI.
Highlights
As predicted, mGluR1-deficient mutant mice exhibit impaired cerebellar long term depression (LTD) [6, 7], there is no disruption of LTD in protein kinase C (PKC)␥-deficient mice [8]
The mGluR1-mediated Ca2ϩ response and LTD induction was greatly reduced in the rostral cerebellum from phospholipase C (PLC)4-deficient mice, an area in which PLC1 and PLC3 were not expressed strongly in these mutant mice
The residual PLC3 activity was sufficient to generate Ca2ϩ elevation and LTD induction. These results suggest that there was a minimum level of PLC3 and PLC4 required to generate the mGluR1-mediated Ca2ϩ response and LTD
Summary
MGluR1-deficient mutant mice exhibit impaired cerebellar LTD [6, 7], there is no disruption of LTD in PKC␥-deficient mice [8]. In PLC4-deficient mice, expression of total PLC, the mGluR1-mediated Ca2؉ response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1– 6). These results suggest that mGluR1-mediated activation of PLC4 in rostral cerebellar Purkinje cells induced LTD via PKC␣ and/or PKCI.
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