Avpr1b agonist-induced synaptic potentiation in CA2 is calcium dependent. (a) Proposed mechanism of Avpr1b-induced potentiation based on the idea that Avpr1b is coupled to Gq proteins and phospholipase C-dependent calcium increases. This mechanism is in contrast to the potentiation induced with antagonists of the CA2-enriched A1 adenosine receptor, which acts through a PKA-dependent pathway. (b) Avpr1b agonist-induced potentiation is blocked by the application of 50 μM AP5, an inhibitor of NMDA receptors (blue circles; n=9) or by temporarily pausing stimulation during drug application (black triangles; n=7), indicating that synaptic glutamate release and NMDA receptors are required for the potentiation. For reference in all the panels, the results of application of d[Leu4,Lys8]-Avp is indicated by the gray squares (n=9). (c) Similarly, loading cells with 15 mM BAPTA, a high affinity calcium chelator, blocked the potentiation induced by 50 nM d[Leu4,Lys8]-Avp (red triangles; n=5), indicating that this potentiation is Ca2+ dependent. In addition, 10 μM KN-62 (orange circles; n=7) and KN-93 (d; green triangles; n=6), inhibitors of CaMKII, included in the recording pipette also inhibited the potentiation. However, KN-92, an inactive analog of KN-93 (brown circles; n=7), 20 μM PKI, an inhibitor of PKA, (magenta circles; n=8, e), or bicuculline, an inhibitor of GABAA receptors (pink circles; n=7, f), failed to block the potentiation. Representative traces are shown as insets at the times indicated by 1 and 2 (scale bars, 50 pA, 20 ms). BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid; NMDA, N-methyl-D-aspartic acid; PKA, protein kinase A.