αCaMKII is essential for cerebellar LTD and motor learning

Activation of postsynaptic alpha-calclum/calmodulin-dependent protein kinase II (alpha CaMKII) 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 UP is unaffected at parallel fiber-Purkinje cell synapses in the cerebellum of alpha CaMKII-/- mice. In contrast, a long-term depression (LTD) protocol resulted in only transient depression in juvenile alpha CaMKII-/- mutants and in robust potentiation in adult mutants. This suggests that the function of alpha CaMKII in parallel fiber-Purkinje cell plasticity is opposite to its function at excitatory hippocampal and cortical synapses. Furthermore, alpha CaMKII-/- 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 alpha CaMKII, our data suggest that an impairment of parallel fiber LTD, while leaving UP intact, is sufficient to disrupt this form of cerebellar learning.