Protein kinase C (PCK) is a family of isoforms that are implicated in subcellular signal transduction. The authors investigated the distribution of several PKC isoforms (PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon) within major cerebellar cell types as well as cerebellar projection target neurons, including Purkinje neurons, cerebellar nuclear neurons, and secondary vestibular neurons. PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon are found within the cerebellum. Of these isoforms, PKC-gamma and PKC-delta are highly expressed in Purkinje cells. PKC-gamma is expressed in all Purkinje cells, whereas the expression of PKC-delta is restricted to sagittal bands of Purkinje cells in the posterior cerebellar cortex. In the lower folia of the uvula and nodulus, Purkinje cell expression of PKC-delta is uniformly high, and the sagittal banding for PKC-delta expression is absent. Within the cerebellar nuclei, PKC-delta-immunolabeled axons terminate within the medial aspect of the caudal half of the ipsilateral interpositus nucleus. PKC delta-immunolabeled axons also terminated within the caudal medial and descending vestibular nuclei (MVN and DVN, respectively), the parasolitary nucleus (Psol), and the nucleus prepositus hypoglossi (NPH). PKC-gamma-immunolabeled axons terminated in all of the cerebellar nuclei as well as in the lateral and superior vestibular nuclei and the MVN, DVN, Psol, and NPH. The projection patterns of PKC-immunolabeled Purkinje cells were confirmed by lesion-depletion studies in which unilateral uvula-nodular lesions caused depletion of PKC-immunolabeled terminals ipsilateral to the lesion in the vestibular complex. These data identify circuitry that is unique to cerebellar-vestibular interactions.

Protein kinase C isoforms PKC-delta and PKC-gamma are expressed in Purkinje cells in the uvula-nodulus of the cerebellum. We examined the effect of Purkinje cell activity on the transcription, expression and intracellular distribution of PKC-delta and PKC-gamma. Relative changes in activity were induced by unilateral labyrinthectomy (UL), decreasing the activity of Purkinje cells on the side of the labyrinthectomy relative to the contralateral side with intact vestibular input. After a UL, there was decreased immunolabeling of Purkinje cell axon terminals in the ipsilateral caudal vestibular complex by antisera to PKC-delta, but not PKC-gamma. Western blots prepared from the uvula-nodulus and caudal vestibular complex showed an increase in the cytosolic PKC-delta and a decrease in membrane-associated PKC-delta in the ipsilateral uvula-nodulus 12-48 h after the UL. Hybridization histochemistry and semiquantitative reverse transcription polymerase chain reaction (RT-PCR) demonstrated no change in transcription of PKC-delta mRNA in the uvula-nodulus 1-240 h after unilateral labyrinthectomy. We conclude that both PKC-delta and PKC-gamma are constitutively expressed in Purkinje cells. The targeting of PKC-delta, but not PKC-gamma, to Purkinje neuron synaptic terminals is influenced by activity.

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