Excessive g-aminobutyric acid (GABA) during brain development may lead to structural and functional changes in the brain tissue. This is the case in succinic semialdehyde dehydrogenase (SSADH) deficiency, which is an inherited neurometabolic disorder of GABA catabolism. Since SSADH participates in the breakdown of GABA, this condition leads to elevated GABA levels, but also increased g-hydroxybutyric acid (GHB) in the brain, which also activates GABA receptors. SSADH deficient patients display neuropsychiatric symptoms, ataxia, and epileptic seizures, and SSADH knock-out mice were recently engineered to model the human disorder. Aims: The purpose of this study was to determine how the SSADH gene dosage impacts single-neuron physiology, since this might offer insight into how SSADH regulates the extracellular GABA levels in physiological and pathophysiological situations. Methods: To investigate the activation of GABA_A receptors in SSADH deficiency, we performed whole- cell patch-clamp recordings in SSADH wild-type, heterozygous, and knock-out mice. Results: Both in dentate gyrus granule cells and interneurons, we found an increase in extrasynaptic GABA_A receptor-mediated tonic current. On the other hand, the frequency and waveform of spontaneous inhibitory postsynaptic currents (sIPSCs) arising from GABAergic activity showed no significant alteration in these cells. Decreases in the SSADH gene dosage led to non- linear increases in GABA_A receptor mediated neurotransmission in these mice. Conclusion: We conclude that SSADH deficiency preferentially leads to increased tonic GABAergic inhibition in the dentate gyrus, which may play a role for the pathophysiological activity in cortical networks.