Down Memory Lane: Psychology professor Pamela Hunt models fetal alcohol spectrum disorders in zebrafish

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ADITHI RAMAKRISHNAN / THE FLAT HAT

Pamela Hunt, professor of psychological sciences, gave the presentation of her life when she was two steps from throwing up.

On the day she was scheduled to give a major presentation at the International Society of Developmental Psychobiology’s annual conference, Hunt woke up feeling nauseous from a meal she’d had the night before. Nerves for the presentation compounded her physical sickness, and when she stepped up to the podium to speak, she warned the audience that she might have to step down for a second to hurl.

“I said, ‘I’m sick, and so if I have to leave the podium, you’ll understand why,’” Hunt said. “I got up, and I gave this talk, and I didn’t remember anything that I said because I just felt so miserable.”

Despite Hunt having no recollection of it, the presentation ended up a resounding success.

“I had one of the most important people in my field come up to me and say, ‘Pam, you should give a talk every time you’re sick, because it was the best talk you’ve ever given,’” Hunt said. “So just don’t worry about it, and get sick before your talks, and it’ll turn out to be good.”

Hunt began teaching at the College of William and Mary in 1997 and set up her research laboratory in August of that year. She has been doing research at the College for 22 years and has had students in her lab since her first semester as a professor. Hunt’s research focuses mainly on memory development in the context of fetal alcohol spectrum disorders, and how alcohol consumption by pregnant mothers can affect cognitive function in their children.

To model human fetal reactions to alcohol exposure, Hunt’s lab conducts memory-testing tasks on zebrafish. Zebrafish have simpler nervous systems with a smaller number of neurons, but their brain cells develop and form connections in ways that are very similar to the human nervous system. It is challenging to look at memory at a cellular level in human brains because of the limitations of imaging technology, but it is possible to do so with zebrafish.

When investigating how best to test memory in the zebrafish, Hunt looked at previously-published papers to see if their procedures could work in her lab. However, there were very few studies conducted with zebrafish as the model organism, and the studies that did exist were not replicable. Hunt’s lab repeated the procedures from several previous studies, but she was unable to get the same results.

“We spent several years trying to replicate other people’s findings, and couldn’t do it,” Hunt said. “We just decided after years of having difficulties to develop our own procedures.”

The lab is currently working on finalizing procedures for two different tasks meant to test memory in zebrafish. The first task involves showing the zebrafish an image on a screen — for example, a red square on a black background — and then showing the fish a video of other zebrafish swimming.

“Zebrafish are social fish; they don’t like to be alone,” Hunt said. “When you present this video of other fish, our test fish swims right over to the monitor and starts swimming up and down as if they are swimming with the other fish.”

The goal of the task is to pair the image of the red square with the video of the other fish swimming; after training, the zebrafish swim to the monitor when the red square is presented, anticipating the video of their friends on the monitor. This is an example of delay conditioning, where the zebrafish are taught to pair a stimulus — in this case, the red square — with a response — swimming up and down with the video of other fish.

To test the zebrafish’s short-term memory, Hunt also uses trace conditioning. Trace conditioning involves the same basic steps with the red square and the video, but with a time delay: The red square flashes on the screen, then disappears, and after a specified time interval, the video of zebrafish swimming plays. With this type of conditioning, the zebrafish learn not only the association between the square and the video, but also must retain the memory of the square during the time delay.

The second task Hunt’s lab is developing for the zebrafish tests a concept known as object recognition. The fish are placed in a tank that contains two identical objects — for example, two beads. They swim around in the tank for a while, acclimating to the environment. Then, after either 24 or 48 hours, the fish are placed in the same tank, which now contains one of the original beads and a new bead. 

“If I show you an object, and then later on, I come and I give you a choice of two objects, do you know which one you’ve seen before?” Hunt said. “Can you point to the novel object? We’re asking the fish that question.”

Zebrafish, like human infants, are more attracted to new objects and experiences, so they tend to swim towards the newer object, spending more time on the side of the tank with the newer bead. Hunt’s lab can measure the time spent by the zebrafish on each side of the tank to see if the fish remember which object they’ve seen before.

Hunt’s lab has collected data for their first task and is currently writing it up for publication; by the end of this year, the lab will finish collecting data on the second task. In February and March, they plan to finish testing their second task, and use the memory tasks to compare cognitive deficits in fish with and without alcohol exposure in their early developmental stages. 

“These are tasks that are variations on tasks that we know kids with fetal alcohol exposure have trouble with,” Hunt said. “They have trouble with memory, and they have trouble with spatial locations, so we’re trying to model that in fish.”

Zebrafish go through early development over a time period of five days, which is significantly different from the nine-month human developmental period. This short time span allows Hunt to keep track of the fish’s neural development and see how alcohol exposure affects the fish at specific stages of brain growth. Hunt hopes to develop and finalize procedures for the memory tasks in her lab to begin experimenting with alcohol exposure. One of the big questions she wants to answer has to do with potential interventions for pregnant mothers who consume alcohol; it isn’t possible to stop all pregnant mothers from drinking, but it might be possible to help the developing children overcome the brain damage done by the alcohol.

“If you can get women to abstain for a short period of time — they’re not going to completely abstain for nine months — but maybe you could get them to abstain for a week here, or a week there,” Hunt said. “Are there critical periods of time that would help the outcome of the offspring? Could we do something to help the kids overcome the alcohol deficit?”