both enhance synaptic transmission at developing neuro- muscular synapses, the two factors may require Ca21 from difference sources, one extracellular and one intracellular. The potentiation of transmitter release usually occurs at least 5–10 min after NT3 application (Figs. 1, 2, and 6; see also Lohof et al., 1993; Xie et al., 1997). This time course implies that NT3-induced Ca21 release modulates the transmitter release mechanisms, rather than contributing directly to the triggering of the exocytosis process. The NT3 modulation is known to be presynaptic in nature (Lo- hof et al., 1993). What are the presynaptic targets down- stream of Ca21 release induced by NT3? CaMKII may serve as an excellent candidate, because its role in trans- mitter release is relatively well-defined (Llinas et al., 1985; Lin et al., 1990; Nichols et al., 1990; Stanton and Gage, 1996; Jin et al., 1998; for review see Greengard et al., 1993). Extensive studies indicate that the activation of CaMKII is triggered by Ca21 influx through extracellular sources. An important finding in this study is that CaMKII can also be activated by Ca21 released from internal stores through IP3 and ryanodine receptors. We showed that even in the complete absence of Ca21 influx, the NT3- induced potentiation of transmitter release can be blocked by the CaMKII inhibitors CaMKII-pep or KN62. Further- more, we found that KN62 can reverse established synap- tic potentiation after NT3 application in Ca21-free me- dium. These results not only provide a link between internal Ca21 stores and CaMKII activation, but also point to CaMKII as a downstream signaling mediator for NT3- induced synaptic potentiation. Since it is difficult to test whether the activation of CaMKII alone is sufficient to mimic the NT3 effect, we can not rule out the possible in- volvement of other processes that may also contribute to the NT3-induced synaptic potentiation. 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