αCaMKII Is Essential for Cerebellar LTD and Motor Learning

Activation of postsynaptic α-calcium/calmodulin-dependent protein kinase II (αCaMKII) by calcium influx is a prerequisite for the induction of long-term potentiation (LTP) at most excitatory synapses in the hippocampus and cortex. Here we show that postsynaptic LTP is unaffected at parallel fiber-Purkinje cell synapses in the cerebellum of αCaMKII-/- mice. In contrast, a long-term depression (LTD) protocol resulted in only transient depression in juvenile αCaMKII-/- mutants and in robust potentiation in adult mutants. This suggests that the function of αCaMKII in parallel fiber-Purkinje cell plasticity is opposite to its function at excitatory hippocampal and cortical synapses. Furthermore, αCaMKII-/- mice showed impaired gain-increase adaptation of both the vestibular ocular reflex and optokinetic reflex. Since Purkinje cells are the only cells in the cerebellum that express αCaMKII, our data suggest that an impairment of parallel fiber LTD, while leaving LTP intact, is sufficient to disrupt this form of cerebellar learning.

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