title: The role of the synthetic enzyme GAD65 in the control of neuronal gamma-aminobutyric acid release.
abstract: 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 gamma-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.
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, CA 94143, USA.
authors.forename: N
authors.initials: N
authors.lastname: Tian
authors.forename: C
authors.initials: C
authors.lastname: Petersen
authors.forename: S
authors.initials: S
authors.lastname: Kash
authors.forename: S
authors.initials: S
authors.lastname: Baekkeskov
authors.forename: D
authors.initials: D
authors.lastname: Copenhagen
authors.forename: R
authors.initials: R
authors.lastname: Nicoll
mesh_terms: D000818:Animals; D005968:Glutamate Decarboxylase / Q000502:physiology*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2