Ca2+-stimulated ADCY1 and ADCY8 regulate distinct aspects of synaptic and cognitive flexibility

The type 1 and 8 adenylyl cyclase (ADCY1 ADCY8) exclusively account for Ca 2+ -stimulated cyclic AMP (cAMP) production regulate activity-dependent synaptic modification. In this study, we examined distinct forms of plasticity in the hippocampus Adcy1 −/− Adcy8 mice. We found that, at Schaffer collateral-CA1 synapses, while mice displayed normal long-term potentiation (LTP) following various induction protocols with high-frequency stimulation (HFS), showed protocol-dependent deficits LTP. also that depression (LTD) requires ADCY1 but not ADCY8. Interestingly, both defective depotentiation (i.e., reversal LTP); were dependent on protocol. Examination spatial memory is required formation initial memory. ADCY8 only formation. These data demonstrate play roles regulating cognitive flexibility involves bidirectional modification function.