That’s because the fish are complex vertebrates, like humans. And like humans, their genome has already been sequenced. That gives the Bard scientists an important tool for mapping how the fish develop, both neurologically and behaviorally. Another advantage is that the fish are transparent in early stages of development, allowing for easy identification and study of normal and abnormal organ growth. First- and second-year ISROP students can begin their study of developmental neurobiology by examining normal growth in the zebrafish, looking specifically at the geneexpression pattern for the NMDA receptor system that’s involved in the development of brain structure. “The students examine when genes turn on after fertilization, how the level of activity changes and in what tissues,” Thomson says. The next step will be disrupting the normal expression of that gene by injecting a morpholino oligonucleotide, a molecular substance that blocks specific gene expression, into the fish eggs, then studying the effects on neurobehavioral development. Bard is one of the few undergraduate institutions to investigate neurotoxicology involving the brain, gene
way as other animals justifies using them as a model,” Scalzo says. “MK-801 studies have been done in rats, but not in zebrafish.” Michal Marszal ’04, who started at Bard as an ISROP student, completed a Senior Project on the role of the NMDA receptor in the early development of the zebrafish brain. Specifically, he detailed the effect MK-801 had on cell death (apoptosis) in the fish. Marszal, who had done research on the NMDA receptor in his native Poland before he came to Bard, says that ISROP and the multidisciplinary nature of the zebrafish work, combining study of both cellular and behavioral effects of the drug, drew him to Bard. He plans to attend medical school. Key to the Bardians’ work, says Scalzo, is the assistance they have received from the Laboratory of Sensory Neuroscience at The Rockefeller University, headed by A. James Hudspeth. In addition, Bard has an ongoing relationship with Rockefeller in which Bard students serve as summer interns at Rockefeller, faculty and postdoctoral fellows from Rockefeller teach courses to Bard students, and Bard faculty and students have access to Rockefeller’s core
Bard is one of the few undergraduate institutions to investigate neurotoxicology involving the brain, gene development, and behavior of the zebrafish.
development, and behavior of the zebrafish. Scalzo’s students are studying how the drug dizocilpine, called MK801, affects the behavior of the fish. In normal development, neurons die when NMDA receptors are overstimulated. MK-801—originally developed as a neuroprotective agent to prevent brain damage from stroke, for example—blocks the receptors, thus preventing neuron death. But it is also a drug that can induce psychosis. Scalzo’s students placed the water-soluble drug into the zebrafish tanks for four days and discovered that it affected the fishes’ activities and learning abilities. For example, while normal zebrafish prefer an “enriched chamber”—containing deeper water, plants, and shiny marbles—the treated fish exhibited no such preference, indicating impaired learning ability. The fish also swam in circles much more frequently when the drug was administered. “Showing that the fish are responsive to this compound in much the same
laboratories. So far, about 50 Bard students have taken part in programs with Rockefeller. What’s next? The Bard scientists have isolated the gene for a protein called NR1, present in all NMDA receptors no matter what the species, a discovery that opens the door to even more research. “Having the gene identified allows us to manipulate it in the test tube, put the altered form back into the zebrafish, and ask how the alterations affect brain development, brain structure, and behavior,” Tibbetts says. Isolation of the zebrafish NR1 gene also was key to the ISROP gene-expression studies. “We are probably the first to do this in zebrafish,” says Tibbetts. “The NR1 gene and protein have been studied in fruit flies, rodents, and people, and we have the zebrafish version.” Bard plans to remain in the forefront of zebrafish exploration, with research in chemistry and computer science possible additions to the multidisciplinary mix. —Cynthia Werthamer
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