Impaired Motor Learning in the Vestibulo-Ocular Reflex in Mice with Multiple Climbing Fiber Input to Cerebellar Purkinje Cells

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Abstract
A unique feature of the cerebellar architecture is that Purkinje cells in the cerebellar cortex each receive input from a single climbing fiber. In mice deficient in the γ isoform of protein kinase C (PKCγ−/−mice), this normal architecture is disrupted so that individual Purkinje cells receive input from multiple climbing fibers. These mice have no other known abnormalities in the cerebellar circuit. Here, we show thatPKCγ−/−mice are profoundly impaired in vestibulo-ocular reflex (VOR) motor learning. ThePKCγ−/−mice exhibited no adaptive increases or decreases in VOR gain at training frequencies of 2 or 0.5 Hz. This impairment was present across a broad range of peak retinal slip speeds during training. We compare the results for VOR motor learning with previous studies of the performance ofPKCγ−/−mice on other cerebellum-dependent learning tasks. Together, the results suggest that single climbing fiber innervation of Purkinje cells is critical for some, but not all, forms of cerebellum-dependent learning, and this may depend on the region of the cerebellum involved, the organization of the relevant neural circuits downstream of the cerebellar cortex, as well as the timing requirements of the learning task.