In college, Eva Pastalkova picked up a library book by the Swiss psychologist Carl Gustav Jung. She was captivated by Jung's ideas on the structure of the psyche and the internal forces behind our thoughts, behaviors, and personalities.
"It was fascinating to me how complex, logical, and powerful processes are 'living' within our psyches, following their own rules and living their own lives, frequently without being noticed or communicated with." Pastalkova wondered whether the tools of neuroscience could be used to study the mechanisms responsible for generating internal brain signals—those that come from inside the brain and are not a result of external cues from the environment.
As a postdoctoral fellow at Rutgers, the State University of New Jersey, Pastalkova helped design an experiment that allows her to do exactly that: investigate the internally generated activity of a rat's brain while the animal is performing a task. Specifically, she studies the activity of hippocampus, the region of the brain responsible for spatial memory—that is, remembering the layout and significance of cues in the environment.
From previous experiments, scientists have known that whenever a rat runs through its environment, individual hippocampal neurons fire sequentially, each for about one second as if to mark a specific segment of a path with a "you are here" sign.
In the new experiment, a rat has been trained to run through a corridor in the shape of an infinity symbol. The animal is rewarded when it alternates between running through the left and right loops of the corridor. The reward is delivered in a small holding area at the midpoint of the two loops.
Between its trips through the maze, the rat must wait for 20 seconds. During this delay period, the animal runs on a wheel, located in the small holding area, and is presumably thinking about what its next choice should be.
Pastalkova and her adviser, György Buzsáki, found that during the delay the hippocampal neurons are activated in a pattern similar to the one that appears when the animal is moving through the environment. Neurons light up sequentially, as if the rat is running through a corridor in its mind.
"While the animal is running on the wheel, all external cues that the animal can see, smell, or hear are stationary. There are no cues in the rat's external environment that can cause any changes in the brain activity," Pastalkova explains.
"It seems like the animal is thinking of running a virtual trajectory. And a different set of neurons are active depending on whether the animal is going to go left or right." Sometimes the brain activity recording is clear enough that Pastalkova knows in real time which direction the animal is going to choose, right from the beginning of the wheel run. "I know beforehand if the rat is going to make a mistake," she says. "It's kind of freaky, to peer into the mind of the rat."
This brain activity, Pastalkova says, is similar to what happens perhaps when a person is walking on a treadmill at the gym after work, tuning out the immediate environment and instead reflecting on the day's past decisions and the plans for tomorrow.
Pastalkova is intrigued that the sequential firing pattern of neurons is generated solely by the brain itself. Many uniquely human cognitive abilities such as decision making, advance planning, and emotional responses must also be generated by internal brain functions. Having found a way to do controlled experiments in animals, she would next like to determine which mechanisms in the brain generate the sequential firing and whether such internally generated activity also can be studied in other brain structures and in different behavioral paradigms.
At Janelia Farm, she will investigate how the network of hippocampal neurons forms these highly organized firing sequences. She will also explore whether she can design an animal experiment to study how emotions are generated. "I know it sounds a little bit crazy," says Pastalkova, "since you cannot put a rat on the therapist's couch and ask it how it is feeling." But she will let a rat's vital signs, such as breathing rate, heart rate, skin conductivity, and muscle tension, define its emotional states throughout a normal day. Such a chart would eventually allow her to make correlations between particular emotions and the brain activity generating them.
Perhaps it's not surprising that it was her father's intense preoccupation with his work as an applied chemist that inspired Pastalkova to become a researcher. She recalls how he used to ponder a research problem during dinner or dash back to the lab over the weekend.
"From his example, I knew that I wanted a job that would be interesting and engage me fully," she explains. And at Janelia she has found just that.
RESEARCH ABSTRACT SUMMARY:
Eva Pastalkova is studying the neuronal mechanisms that generate brain activity internally, while a rat performs a cognitive task. The influence of the external stimuli on the recorded activity is eliminated by making the stimuli stationary or irrelevant.
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Photo: Pascale Quilichini