Abstract
The zebrafish camouflage response is an innate "hard-wired" behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both adenylyl cyclase 5 and extracellular signal-regulated kinase (ERK) is required for such ethanol-induced or light-induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP-dependent and ERK-dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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Adaptation, Physiological / drug effects*
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Adenylyl Cyclases / metabolism
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Analysis of Variance
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Animals
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Animals, Genetically Modified
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Behavior, Animal / drug effects
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Brain / growth & development
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Brain / metabolism
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Cells, Cultured
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Central Nervous System Depressants / pharmacology*
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Colforsin / pharmacology
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Corticotropin-Releasing Hormone / metabolism*
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Corticotropin-Releasing Hormone / pharmacology
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Defense Mechanisms*
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Drug Interactions
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Enzyme Inhibitors / pharmacology
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Ethanol / pharmacology*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Larva
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Light*
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Melanocytes / drug effects
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Mutation
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Nystagmus, Optokinetic / drug effects
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Nystagmus, Optokinetic / genetics
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Oligodeoxyribonucleotides, Antisense / pharmacology
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Pro-Opiomelanocortin / pharmacology
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Receptors, Corticotropin-Releasing Hormone / genetics
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Receptors, Corticotropin-Releasing Hormone / metabolism
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Skin / cytology
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Time Factors
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Zebrafish
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Zebrafish Proteins / genetics
Substances
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Central Nervous System Depressants
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Enzyme Inhibitors
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Oligodeoxyribonucleotides, Antisense
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Receptors, Corticotropin-Releasing Hormone
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Zebrafish Proteins
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Colforsin
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Ethanol
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Pro-Opiomelanocortin
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Corticotropin-Releasing Hormone
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Extracellular Signal-Regulated MAP Kinases
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Adenylyl Cyclases
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adenylyl cyclase type V
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1-Methyl-3-isobutylxanthine