RT Journal Article SR Electronic T1 Upregulation of GABA Neurotransmission Suppresses Hippocampal Excitability and Prevents Long-Term Potentiation in Transgenic Superoxide Dismutase-Overexpressing Mice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 10977 OP 10984 DO 10.1523/JNEUROSCI.19-24-10977.1999 VO 19 IS 24 A1 Levkovitz, Y. A1 Avignone, E. A1 Groner, Y. A1 Segal, M. YR 1999 UL http://www.jneurosci.org/content/19/24/10977.abstract AB Cu/Zn superoxide dismutase (SOD-1) is a key enzyme in oxygen metabolism in the brain. Overexpression of SOD-1 in transgenic (Tg) mice has been used to study the functional roles of this enzyme in oxidative stress, lipid peroxidation, and neurotoxicity. We found that Tg-SOD-1 mice are strikingly less sensitive to kainic acid-induced behavioral seizures than control mice. Furthermore, the hippocampus of Tg-SOD-1 mice was far less sensitive to local application of bicuculline, a GABA-A antagonist, than the hippocampus of control mice. GABAergic functions, expressed in extracellular paired-pulse depression, and in IPSCs recorded in dentate granular cells were enhanced in Tg-SOD-1 mice. Finally, long-term potentiation (LTP), not found in the dentate gyrus of Tg-SOD-1 mice, could be restored by local blockade of inhibition and could be blocked in control mice by injection of diazepam, which amplifies inhibition. These results indicate that constitutive elevation of SOD-1 activity exerts a major effect on neuronal excitability in the hippocampus, which, in turn, controls hippocampal ability to express LTP.