Aims: Sortilin is a member of the Vps10p domain receptor family, which is involved in the intracellular sorting secretion and signaling of brain derived neurotrophic factor (BDNF). The aim of this study was to reveal an impact of sortilin deficiency on the shaping of the GABA_A receptor mediated inhibition in the dentate gyrus. Methods: In acute brain slices of adult wild type (WT) and sortilin knock-out (KO) mice, whole-cell patch-clamp recordings were made from dentate gyrus granule cells (DGGCs). We quantified (1) the frequency of inhibitory postsynaptic currents (IPSCs) recorded from DGGCs; (2) paired-pulse depression of IPSCs evoked by minimal stimulation of GABAergic fibers; (3) immunohistochemically stained sections to compare the total number of parvalbumin-positive interneurons (PVIs) in dentate gyrus of WT and sortilin KO. Results: We found a significant increase in the frequency of spontaneous IPSCs from 2.4 ± 0.4 (n = 16) in WT to 5.3 ± 0.8 (n = 18) Hz in KO (p < 0.01). On the other hand, the frequency of miniature IPSCs recorded in TTX was less affected and reached 1.8 ± 0.2 Hz in WT (n = 11) and 2.3 ± 0.5 Hz in KO (n = 16). Paired-pulse depression of evoked IPSCs was increased in sortilin KO mice, indicating that the GABA release probability was higher in KOs. The number of PVIs in the dentate gyrus showed no difference between KO and WT. Acute wash in of BDNF (20 g/ml) reduced GABAergic inhibition in KOs. Finally, incubation of the brain slices with scavenger of an endogenous BDNF, tyrosine receptor kinase B-immunoglobulin G (TrkB-Fc) failed to affect frequency of sIPSCs in KO mice, while significantly increasing sIPSCs in WT to 5.1 ± 0.9 Hz (n = 9). Conclusion: Our data suggest that sortilin deficiency leads to an increase in synaptic GABAergic inhibition, which is not associated with changes in the number of parvalbumin-positive interneurons. We suggest that lack of sortilin impairs the BDNF signaling pathway, leading to presynaptic disinhibition and increased excitability of GABAergic interneurons of the dentate gyrus.