Brain-derived neurotrophic factor (BDNF) is an important signaling molecule in the mammalian central nervous system (CNS), which plays a crucial role for the proper development and function of neuronal networks in the CNS. BDNF is synthesized in a pro-form by neurons, which is cleaved into mature BDNF in the extracellular space. It was recently demonstrated that both proBDNF and mature BDNF can be released by hippocampal neurons, and exert opposite effects on synaptic plasticity. Thus, release of proBDNF favors long-term depression via p75NTR at excitatory synapses, while mature BDNF favors TrkB-dependent long-term potentiation in the hippocampus. Here, we investigated whether proBDNF and mature BDNF exert differential effects on the GABAergic system. Using patch-clamp recordings in mouse brain slices, we recorded GABAergic inhibitory input onto dentate gyrus granule cells that arise from local interneuron networks. In addition, we did direct recordings from fast-spiking parvalbumin-positive interneurons. We found that mature BDNF, but not proBDNF, depressed the excitability of fast-spiking interneurons in the dentate gyrus. This was accompanied by a decrease in spontaneous inhibitory postsynaptic currents by 57 +/­ 16% in the postsynaptic cells. The effect of mature BDNF on GABAergic inhibition was inhibited by soluble TrkB-Fc and the TrkB blocker K-252a. Also, TrkB protein could be immunohistochemically detected in parvalbumin-positive interneurons. Finally, the proBDNF receptor p75NTR was not expressed in interneurons, an observation that is in accordance with the inability of proBDNF to modulate GABAergic activity. Altogether, this suggests that mature BDNF, but not proBDNF, reduces the excitability of the interneuron network via TrkB.