Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that, when raised by forskolin, induces long-term potentiation (LTP) of synaptic transmission and expression of immediate early genes such as FOS by activating the postsynaptic PKA-CREB pathway. However, most studies have relied on pharmacological tools whose actions are not confined to specific cells or synaptic compartments. Here, we use photoactivatable adenylyl cyclases to raise cAMP in single postsynaptic hippocampal CA1 neurons, in many presynaptic CA3 or postsynaptic CA1 neurons or in all excitatory neurons to investigate cell-autonomous and synaptic compartment-specific effects of cAMP.Surprisingly, optogenetically raising cAMP in single postsynaptic CA1 neurons induced neither LTP nor FOS expression despite PKA activation. However, similarly to forskolin, increasing cAMP in excitatory neurons throughout the whole slice did induce LTP and strong FOS expression. Interestingly, raising cAMP in only presynaptic or postsynaptic neurons induced weaker LTP, while increasing the intensity of FOS labeling to similar levels as when cAMP is stimulated throughout the whole hippocampal slice. Furthermore, blocking the activity of typical cAMP downstream effectors such as PKA, EPAC and HCN channels only partially reduced the intensity of FOS labeling.In conclusion, in contrast to current models of intracellular signaling cascades, there is no direct pathway leading from cAMP to FOS induction in individual neurons not to LTP. Rather cAMP increases excitability and transmitter release and these are required for FOS and LTP. The function of neuronal cAMP as a plasticity trigger thus requires an intact, synaptically connected network.