Toxic Responses of the Fish Nervous System

General anaesthetics are much more selective than is usually appreciated and may act by binding to only a small number of targets in the central nervous system. At surgical concentrations their principal effects are on ligand-gated (rather than voltage-gated) ion channels, with potentiation of postsynaptic inhibitory channel activity best fitting the pharmacological profile observed in general anaesthesia. Although the role of second messengers remains uncertain, it is now clear that anaesthetics act directly on proteins rather than on lipids.

Zebra fish may be an ideal vertebrate model system for numerous human diseases with which the genetics and biological mechanisms of the disease may be studied. Zebra fish has been successfully used in developmental genetics, and recently, neurobiologists have also started to study this species. A potentially interesting target disease amenable for analysis with zebra fish is drug addiction, e.g. alcoholism. Although genetic tools to manipulate the genome of zebra fish are available, appropriate phenotypical testing methods are often lacking. In this paper, we describe basic behavioral tests to investigate the acute effects of alcohol on zebra fish. These behavioral paradigms will be useful for the genetic and biological analysis of acute and chronic drug effects as well as addiction. In addition to presenting findings for the acute effects of alcohol, we briefly describe our strategy for generating and screening mutants. We hope that our pilot work will facilitate the future development of behavioral tests and the use of zebra fish in the genetic analysis of the biological effects of drugs of abuse.

The formation of synapses in the vertebrate central nervous system is a complex process that occurs over a protracted period of development. Recent work has begun to unravel the mysteries of synaptogenesis, demonstrating the existence of multiple molecules that influence not only when and where synapses form but also synaptic specificity and stability. Some of these molecules act at a distance, steering axons to their correct receptive fields and promoting neuronal differentiation and maturation, whereas others act at the time of contact, providing positional information about the appropriateness of targets and/or inductive signals that trigger the cascade of events leading to synapse formation. In addition, correlated synaptic activity provides critical information about the appropriateness of synaptic connections, thereby influencing synapse stability and elimination. Although synapse formation and elimination are hallmarks of early development, these processes are also fundamental to learning, memory, and cognition in the mature brain.