PUBLICATION
Ethanol-modulated camouflage response screen in zebrafish uncovers a novel role for cAMP and extracellular signal-regulated kinase signaling in behavioral sensitivity to ethanol
- Authors
- Peng, J., Wagle, M., Mueller, T., Mathur, P., Lockwood, B.L., Bretaud, S., and Guo, S.
- ID
- ZDB-PUB-090706-21
- 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.
Citation
Peng, J., Wagle, M., Mueller, T., Mathur, P., Lockwood, B.L., Bretaud, S., and Guo, S. (2009) Ethanol-modulated camouflage response screen in zebrafish uncovers a novel role for cAMP and extracellular signal-regulated kinase signaling in behavioral sensitivity to ethanol. The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(26):8408-8418.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping