Abstract

Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio) model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined. Differences between human and zebrafish neurochemical pathways are highlighted. We also review techniques for evaluating neurological function, including the measurement of neurotransmitter levels, assessment of gene expression through transcriptomic analysis, and the recording of neurobehavior. Finally examples of chemical toxicity studies evaluating alterations in neurotransmitter systems in the zebrafish model are reviewed.

Highlights

  • Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning and memory, and even maintenance of life

  • Two Th encoding paralogs were identified in teleosts, th1 and th2 [112]. th1-negative, th2-positive neurons were identified in zebrafish brain [113,114,115] and these neurons appeared to be immunoreactive for slc18a2, aaad, and slc6a3, consistent with a dopaminergic phenotype, it was discovered that the gene encoded by th2 appears to function as a tryptophan hydroxylase when isolated in vitro [115,116]

  • Once ACh has been synthesized by choline acetyltransferase (ChAT) it is packaged into vesicles by vesicular ACh transporter (VAChT) which is coded by SLC18A3 [106]

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Summary

Introduction

Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning and memory, and even maintenance of life. Zebrafish share the common neurotransmitter pathways with mammals and have similar neuroanatomy in many areas such as the spinal cord, hindbrain and retina, but as the brain develops by eversion rather than inversion, some classical regions of the mammalian brain, such as the hippocampus, amygdala, and substantia nigra, are not present as such in zebrafish. The function of these areas appears to be maintained elsewhere in the brain, allowing functional comparisons between zebrafish and mammals [14]. This review includes new research findings published since the last reviews on zebrafish neurochemistry, updated terminology, and aims to serve as a reference for the major neurotransmitter systems

Zebrafish as a Biomedical Model
Review of Neurotransmitter Systems
Glutamate
Catecholamines
Distribution
Serotonin
Acetylcholine
Histamine
Glycine
Other Neurotransmitters
Evaluation of Neurotoxicity
Evaluation of Neurotransmitters
Evaluation of Gene Expression Changes in Neurotransmitter Pathways
Evaluation of Neurobehavior
Visualization of Neurotransmitters and Neurotransmitter Systems
Pharmacology Screens
Specific Examples of Chemical Toxicity Targeting Neurotransmitter Systems
Pesticides
Metals
Conclusions
Methods
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