title: Ancient Anxiety Pathways Influence Drosophila Defense Behaviors.
abstract: Anxiety helps us anticipate and assess potential danger in ambiguous situations [1-3]; however, the anxiety disorders are the most prevalent class of psychiatric illness [4-6]. Emotional states are shared between humans and other animals [7], as observed by behavioral manifestations [8], physiological responses [9], and gene conservation [10]. Anxiety research makes wide use of three rodent behavioral assays-elevated plus maze, open field, and light/dark box-that present a choice between sheltered and exposed regions [11]. Exposure avoidance in anxiety-related defense behaviors was confirmed to be a correlate of rodent anxiety by treatment with known anxiety-altering agents [12-14] and is now used to characterize anxiety systems. Modeling anxiety with a small neurogenetic animal would further aid the elucidation of its neuronal and molecular bases. Drosophila neurogenetics research has elucidated the mechanisms of fundamental behaviors and implicated genes that are often orthologous across species. In an enclosed arena, flies stay close to the walls during spontaneous locomotion [15, 16], a behavior proposed to be related to anxiety [17]. We tested this hypothesis with manipulations of the GABA receptor, serotonin signaling, and stress. The effects of these interventions were strikingly concordant with rodent anxiety, verifying that these behaviors report on an anxiety-like state. Application of this method was able to identify several new fly anxiety genes. The presence of conserved neurogenetic pathways in the insect brain identifies Drosophila as an attractive genetic model for the study of anxiety and anxiety-related disorders, complementing existing rodent systems.
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore 138673, Singapore; Institute for Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore.
authors.forename: Farhan
authors.initials: F
authors.lastname: Mohammad
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore.
authors.forename: Sameer
authors.initials: S
authors.lastname: Aryal
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore.
authors.forename: Joses
authors.initials: J
authors.lastname: Ho
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore.
authors.forename: James Charles
authors.initials: JC
authors.lastname: Stewart
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore.
authors.forename: Nurul Ayuni
authors.initials: NA
authors.lastname: Norman
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore.
authors.forename: Teng Li
authors.initials: TL
authors.lastname: Tan
authors.affiliation: Institute for Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore.
authors.forename: Agnese
authors.initials: A
authors.lastname: Eisaka
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore 138673, Singapore; Institute for Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore; Department of Physiology, National University of Singapore, Singapore 138673, Singapore. Electronic address: claridge-chang.adam@duke-nus.edu.sg.
authors.forename: Adam
authors.initials: A
authors.lastname: Claridge-Chang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D004330:Drosophila; D008027:Light; D051379:Mice; D009434:Neural Pathways; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D044282:Receptor, Serotonin, 5-HT1A; D003975:Diazepam