Deletion of the ryanodine receptor type 3 (RyR3) impairs forms of synapticplasticity and spatial learning

Deletion of the ryanodine receptor type 3 (RyR3) results in specific change s in hippocampal synaptic plasticity, without affecting hippocampal morphol ogy, basal synaptic transmission or presynaptic function. Robust long-term potentiation (LTP) induced by repeated, strong tetanization in the CA1 regi on and in the dentate gyrus was unaltered in hippocampal slices iii vitro, whereas weak forms of plasticity generated by either a single weak tetaniza tion or depotentiation of a robust LTP were impaired. These distinct physio logical deficits were paralleled by a reduced flexibility in relearning a n ew target in the water-maze. In contrast, learning performance in the acqui sition phase and during probe trial did not differ between the mutants and their wild-type littermates. In the open-field, RyR3(-/-) mice displayed a normal exploration and habituation, but had an increased speed of locomotio n and a mild tendency to circular running. The observed physiological and b ehavioral effects implicate RyR3-mediated Ca2+ release in the intracellular processes underlying spatial learning and hippocampal synaptic plasticity.