To determine the in vivo targets of long-lasting actions of TrkB signaling on synaptic function we analyze synaptic components of excitatory and inhibitory circuits in the cerebral cortex of trkB (−/−) mice. First, we show that K +-evoked glutamate and GABA release from forebrain mutant synaptosomes was decreased. Moreover, the dependence of regulated exocytosis on the SNARE SNAP-25 and the Ca 2+-dependent neurotransmitter release were also impaired in trkB (−/−) mice. We also analyzed postsynaptic glutamate and GABA A ionotropic receptors in cortical areas of trkB mutant mice. By using Western blot we observed decreased levels of the AMPA receptor subunits GluR2/3 and GluR4 in trkB (−/−) forebrains. In contrast, the forebrain of mutant mice exhibited increased levels of the GABA A receptor subunit α3 and α5 and a reduction of the γ2 subunit. Immunocytochemical analysis showed that the hippocampus and neocortex of mutant mice exhibited decreased numbers of interneurons positive for distinct AMPA and GABA A receptor subunits. Furthermore, alteration of inhibitory circuits in trkB (−/−) mice was also shown by the low expression of the GABA-synthesizing enzyme glutamic acid decarboxylase in mutant cortical areas. The present results indicate that long-lasting TrkB signaling is required for the precise adjustment of neurotransmitter release and for the correct composition of the fast glutamatergic and GABAergic receptor subunits in vivo.