Cellular/Molecular CalciumMicrodomains Near R-Type Calcium Channels Control the Induction of Presynaptic Long-Term Potentiation at Parallel Fiber to Purkinje Cell Synapses

R-type calcium channels in postsynaptic spines signal through functional calcium microdomains to regulate a calcium/calmodulin-sensitive potassium channel that in turn regulates postsynaptic hippocampal long-termpotentiation (LTP). Here, we askwhether R-type calcium channels in presynaptic terminals also signal through calciummicrodomains to control presynaptic LTP. We focus on presyn-aptic LTP at parallel fiber to Purkinje cell synapses in the cerebellum (PF-LTP), which is mediated by calcium/calmodulin-stimulated adenylyl cyclases. Althoughmost presynaptic calcium influx is through N-type and P/Q-type calcium channels, blocking these channels does not disrupt PF-LTP, but blocking R-type calcium channels does.Moreover, global calcium signaling cannot account for the calcium dependence of PF-LTP because R-type channels contribute modestly to overall calcium entry. These findings indicate that, within presynaptic terminals,R-type calciumchannelsproduce calciummicrodomains that evokepresynapticLTPatmoderate frequencies that do not greatly increase global calcium levels