ZFIN ID: ZDB-PUB-090706-21
Ethanol-modulated camouflage response screen in zebrafish uncovers a novel role for cAMP and extracellular signal-regulated kinase signaling in behavioral sensitivity to ethanol
Peng, J., Wagle, M., Mueller, T., Mathur, P., Lockwood, B.L., Bretaud, S., and Guo, S.
Date: 2009
Source: The Journal of neuroscience : the official journal of the Society for Neuroscience   29(26): 8408-8418 (Journal)
Registered Authors: Guo, Su, Mathur, Priya, Mueller, Thomas, Peng, Jisong, Wagle, Mahendra
Keywords: none
MeSH Terms:
  • Adenylyl Cyclases/genetics
  • Adenylyl Cyclases/metabolism
  • Adrenocorticotropic Hormone/metabolism
  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal/drug effects*
  • Behavior, Animal/physiology
  • Brain/anatomy & histology
  • Brain/drug effects
  • Brain/growth & development
  • Brain/metabolism
  • Central Nervous System Depressants/pharmacology*
  • Chromosome Mapping/methods
  • Cyclic AMP/genetics
  • Cyclic AMP/metabolism*
  • Darkness
  • Dose-Response Relationship, Drug
  • ELAV Proteins/metabolism
  • Ethanol/pharmacology*
  • Extracellular Signal-Regulated MAP Kinases/genetics
  • Extracellular Signal-Regulated MAP Kinases/metabolism*
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/genetics
  • Green Fluorescent Proteins/genetics
  • Isoenzymes/genetics
  • Isoenzymes/metabolism
  • Larva
  • Light
  • Locomotion/drug effects
  • Locomotion/genetics
  • Melanosomes/drug effects
  • Mutation/genetics
  • Phosphorylation/drug effects
  • Reaction Time/drug effects
  • Signal Transduction/drug effects*
  • Signal Transduction/genetics
  • Spatial Behavior/drug effects
  • Spatial Behavior/physiology
  • Zebrafish/genetics*
  • Zebrafish/physiology
PubMed: 19571131 Full text @ J. Neurosci.
Ethanol, a widely abused substance, elicits evolutionarily conserved behavioral responses in a concentration-dependent manner in vivo. The molecular mechanisms underlying such behavioral sensitivity to ethanol are poorly understood. While locomotor-based behavioral genetic screening is successful in identifying genes in invertebrate models, such complex behavior-based screening has proven difficult for recovering genes in vertebrates. Here we report a novel and tractable ethanol response in zebrafish. Using this ethanol-modulated camouflage response as a screening assay, we have identified a zebrafish mutant named fantasma (fan), which displays reduced behavioral sensitivity to ethanol. Positional cloning reveals that fan encodes type 5 adenylyl cyclase (AC5). fan/ac5 is required to maintain the phosphorylation of extracellular signal-regulated kinase (ERK) in the forebrain structures, including the telencephalon and hypothalamus. Partial inhibition of phosphorylation of ERK in wild-type zebrafish mimics the reduction in sensitivity to stimulatory effects of ethanol observed in the fan mutant, whereas, strikingly, strong inhibition of phosphorylation of ERK renders a stimulatory dose of ethanol sedating. Since previous studies in Drosophila and mice show a role of cAMP signaling in suppressing behavioral sensitivity to ethanol, our findings reveal a novel, isoform-specific role of AC signaling in promoting ethanol sensitivity, and suggest that the phosphorylation level of the downstream effector ERK is a critical "gatekeeper" of behavioral sensitivity to ethanol.