Researchers at the Perelman School of Medicine at the University of Pennsylvaniadescribe the first set of genes important in learning in a zebrafish model in the journal Neuron this week. “Using an in-depth analysis of one of these genes, we have already revealed an important relevant signaling pathway,” says senior author Michael Granato, PhD, a professor of Cell and Developmental Biology. “The proteins in this pathway could provide new insights into the development of novel pharmacological targets.”

Over the last 20 years, zebrafish have become great models for studying development and disease. Like humans, zebrafish are vertebrates and over 80 percent of human genes bearing disease descriptions are also present in zebrafish. As such, this animal model has become increasingly popular to study human diseases such as cardiovascular conditions or tumor formation. 

Zebrafish have also become an ideal model for studying vertebrate neuroscience and behavior. In fact, Granato developed the first high-throughput behavioral assays that measure learning and memory in fish. “Normal fish startle with changes in noise and light level by bending and swimming away from the annoying stimuli. They do eventually habituate and get used to the alterations in their environment,” he explains. “However, fish mutants fail to habituate -- they never get used to their surroundings and always flinch at the loud noises.” 

In nature, this startle response is important for avoiding predators, but is flexible in how the fish use it in different situations, notes first author Marc A. Wolman, PhD, a postdoctoral fellow in the Granato lab who is now an assistant professor at the University of Wisconsin. Past data from the Granato lab indicate that learning and memory defects are reversible with acute pharmacologic treatments and are therefore not hard-wired, as might be expected for a defect in the development of nerves. Habituation represents a fundamental form of learning, yet the underlying molecular genetic mechanisms are not well defined. In humans, deficits in habituation are associated with a variety of neuropsychiatric disorders, including schizophrenia, autism, Tourette’s, and obsessive-compulsive disorder.

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