title: GABA receptors containing Rdl subunits mediate fast inhibitory synaptic transmission in Drosophila neurons.
abstract: GABAergic inhibition in Drosophila, as in other insects and mammals, is important for regulation of activity in the CNS. However, the functional properties of synaptic GABA receptors in Drosophila have not been described. Here, we report that spontaneous GABAergic postsynaptic currents (sPSCs) in cultured embryonic Drosophila neurons are mediated by picrotoxin-sensitive chloride-conducting receptors. A rapid increase in spontaneous firing in response to bath application of picrotoxin demonstrates that these GABA receptors mediate inhibition in the neuronal networks formed in culture. Many of the spontaneous GABAergic synaptic currents are sodium action potential independent [miniature IPSCs (mIPSCs)] but are regulated by external calcium levels. The large variation in mIPSC frequency, amplitude, and kinetics properties between neurons suggests heterogeneity in GABA receptor number, location, and/or subtype. A decrease in the mean mIPSC decay time constant between 2 and 5 d, in the absence of a correlated change in rise time, demonstrates that the functional properties of the synaptic GABA receptors are regulated during maturation in vitro. Finally, neurons from the GABA receptor subunit mutant Rdl exhibit reduced sensitivity to picrotoxin blockade of the mIPSCs and resistance to picrotoxin-induced increases in spontaneous firing frequency. This demonstrates that Rdl containing GABA receptors play a direct role in mediating synaptic inhibition in Drosophila neural circuits formed in culture.
authors.affiliation: Departments of Anatomy and Neurobiology, Developmental and Cell Biology, University of California, Irvine, California 92697-1280.
authors.forename: Daewoo
authors.initials: D
authors.lastname: Lee
authors.forename: Hailing
authors.initials: H
authors.lastname: Su
authors.forename: Diane K
authors.initials: DK
authors.lastname: O'Dowd
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000294:innervation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002118:Calcium; D015220:Calcium Channels; D018118:Chloride Channels; D002712:Chlorides; D029721:Drosophila Proteins; D018756:GABA Antagonists; D010852:Picrotoxin; D021122:Protein Subunits; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C082030:Rdl protein, Drosophila