The secreted form of β-amyloid precursor protein (sAPPα) is released from neurons in an activity-dependent manner, and has been reported to modulate neuronal excitability in dissociated hippocampal neurons. We now report that sAPPα shifts the frequency dependence for induction of long- term depression of synaptic transmission (LTD) in hippocampal slices from adult rats. Whereas low frequency stimulation (1 Hz) of Schaffer collateral axons induced LTD of the post-synaptic response of CA1 neurons in control slices, it did not induce LTD in slices pretreated with sAPPα. On the other hand, whereas a 10 Hz stimulation normally induced neither LTD or LTP, it did induce LTD in slices pretreated with sAPPα. sAPPα potentiated LTP induced by high frequency stimulation. sAPPα induced cGMP production in hippocampal slices, and pretreatment of slices with 8-bromo-cyclic GMP mimicked the effect of sAPPα on LTD suggesting a role for cyclic GMP in modulation of LTD. The data suggest an important role for sAPPα in modulation of synaptic plasticity in the hippocampus.
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