mGluR7 activation and surface expression regulates bidirectional plasticity of feedforward inhibition in the hippocampal mossy fiber (MF) pathway. At naïve MF inputs to stratum lucidum interneurons (SLINs) surface mGluR7 activation during high-frequency stimulation (HFS) yields presynaptic long-term depression (LTD) through a PKC-dependent mechanism. This activity-induced LTD is mimicked by pairing basal synaptic stimulation with mGluR7 activation by exogenously applied agonist (L-AP4, 400 mM for 5 minutes). Surprisingly, L-AP4-induced LTD does not simply occlude HFS-induced LTD but rather unmasks the ability of HFS to induce presynaptic MF-SLIN long-term potentiation (LTP). We now demonstrate that L-AP4-induced LTD unlocks the ability of MF-SLIN inputs to enhance release in response to increased cAMP levels. As previously reported transmission at naïve MF-SLIN synapses was not significantly affected by forskolin treatment (50-100 mM for 5 minutes) remaining at 87% of control transmission assayed prior to forskolin application (n = 4). In contrast, following L-AP4-induced MF-SLIN LTD to 63% of control responses, forskolin returned (de-depressed) MF-SLIN EPSCs to 142% of control responses (n = 7). Finally, we found that conversion of depressing MF-SLIN inputs to potentiating ones is also revealed with multiple rounds of HFS. After two rounds of HFS MF-SLIN EPSCs were reduced to 55% of control responses (obtained prior to any HFS), but following subsequent HFS EPSCs de-depressed to 99% of initial control values measured prior to any HFS conditioning stimulation. We propose that MF-SLIN LTP proceeds by a cAMP-dependent cascade that can only be engaged following agonist-induced mGluR7 sequestration from MF-SLIN terminals, yielding state-dependent cAMP sensitivity of MF-SLIN transmission.