Hippocampal CA1 pyramidal neurons receive excitatory inputs from both ipsi- and contralateral CA3 and CA2 regions. While synaptic plasticity at the intrahippocampal Schaffer collateral synapses has been extensively described, synaptic plasticity mechanisms at interhippocampal commissural fiber synapses are less well understood. In this project, we investigate cyclic adenosine monophosphate (cAMP)-dependent plasticity at commissural synapses in the CA1 region. We performed in vivo stereotactic injections of AAVs to express ChrimsonR unilaterally in CA3/CA2 glutamatergic neurons of one hippocampus. ChrimsonR, a red-light sensitive Channelrhodopsin, allows us to trigger transmitter release with short orange light flashes selectively at ipsi- or contralateral synapses in acute brain slices. We then induced cAMP production either pharmacologically by application of forskolin, or optically by blue light-stimulation of the light-activated adenylyl cyclase bPAC, which we coexpressed with ChrimsonR to achieve specific presynaptic manipulation of cAMP. Both the pharmacological stimulation of endogenous adenylyl cyclases with forskolin and the activation of bPAC enhanced synaptic transmission at commissural fiber synapses. Therefore, we propose that commissural synapses in CA1 express a presynaptic, cyclic adenosine monophosphate (cAMP)-dependent form of plasticity. It remains to be investigated from which specific cell population or network these cAMP-sensitive synapses originate, and further research is needed to uncover the intricate mechanisms and functions underlying this phenomenon.