The role of the synthetic enzyme GAD65 in the control of neuronal γ-aminobutyric acid release

• DOI: 10.1073/pnas.96.22.12911
• Publication Date: 2002-07-26T14:35:07Z
• Authors: Ning Tian; Carl Petersen; Shera Kash; Steinunn Baekkeskov; David Copenhagen; Roger Nicoll
• Keywords: Neurons; Glutamate Decarboxylase; In Vitro Techniques; Isoenzymes; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 0302 clinical medicine; Mice, Inbred NOD; Synapses; Animals; gamma-Aminobutyric Acid

We have studied GABAergic synaptic transmission in retinal ganglion cells and hippocampal pyramidal cells to determine, at a cellular level, what is the effect of the targeted disruption of the gene encoding the synthetic enzyme GAD65 on the synaptic release of γ-aminobutyric acid (GABA). Neither the size nor the frequency of GABA-mediated spontaneous inhibitory postsynaptic currents (IPSCs) were reduced in retina or hippocampus in GAD65−/− mice. However, the release of GABA during sustained synaptic activation was substantially reduced. In the retina both electrical- and K + -induced increases in IPSC frequency were depressed without a change in IPSC amplitude. In the hippocampus the transient increase in the probability of inhibitory transmitter release associated with posttetanic potentiation was absent in the GAD65−/− mice. These results indicate that during and immediately after sustained stimulation the increase in the probability of transmitter release is not maintained in GAD65−/− mice. Such a finding suggests a decrease in the size or refilling kinetics of the releasable pool of vesicles, and various mechanisms are discussed that could account for such a defect.