title: Mutation of the Drosophila vesicular GABA transporter disrupts visual figure detection.
abstract: The role of gamma amino butyric acid (GABA) release and inhibitory neurotransmission in regulating most behaviors remains unclear. The vesicular GABA transporter (VGAT) is required for the storage of GABA in synaptic vesicles and provides a potentially useful probe for inhibitory circuits. However, specific pharmacologic agents for VGAT are not available, and VGAT knockout mice are embryonically lethal, thus precluding behavioral studies. We have identified the Drosophila ortholog of the vesicular GABA transporter gene (which we refer to as dVGAT), immunocytologically mapped dVGAT protein expression in the larva and adult and characterized a dVGAT(minos) mutant allele. dVGAT is embryonically lethal and we do not detect residual dVGAT expression, suggesting that it is either a strong hypomorph or a null. To investigate the function of VGAT and GABA signaling in adult visual flight behavior, we have selectively rescued the dVGAT mutant during development. We show that reduced GABA release does not compromise the active optomotor control of wide-field pattern motion. Conversely, reduced dVGAT expression disrupts normal object tracking and figure-ground discrimination. These results demonstrate that visual behaviors are segregated by the level of GABA signaling in flies, and more generally establish dVGAT as a model to study the contribution of GABA release to other complex behaviors.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Fei
authors.forename: Dawnis M
authors.initials: DM
authors.lastname: Chow
authors.forename: Audrey
authors.initials: A
authors.lastname: Chen
authors.forename: Rafael
authors.initials: R
authors.lastname: Romero-Calderón
authors.forename: Wei S
authors.initials: WS
authors.lastname: Ong
authors.forename: Larry C
authors.initials: LC
authors.lastname: Ackerson
authors.forename: Nigel T
authors.initials: NT
authors.lastname: Maidment
authors.forename: Julie H
authors.initials: JH
authors.lastname: Simpson
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.forename: David E
authors.initials: DE
authors.lastname: Krantz
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000166:cytology / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005403:Fixation, Ocular / Q000502:physiology; D005724:Ganglia / Q000166:cytology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D007814:Larva / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009068:Movement / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D021381:Protein Transport; D013572:Synaptic Vesicles / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014796:Visual Perception / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C493406:vesicular GABA transporter