When asked in kindergarten what she wanted to be when she grew up, Skylar Fang recalls saying, “I want to be a scientist.”
Little did she know that this childhood aspiration would lead her on a path driven by a deep curiosity about animal behaviours and the mysteries of the brain. During her undergrad, she studied Biological Sciences at Zhejiang University, later transferring to Cornell where she pursued a double major in Biological Sciences, Biometry & Statistics.
Today, Skylar Fang is a PhD student under the supervision of Dr. Manu Madhav in the NC4 lab. Her interest in systems and computational neuroscience led to her thesis project, where she is studying flexible hippocampal representations using an apparatus called the Dome.
What is the Dome?
The Dome is a groundbreaking piece of equipment designed by Dr. Madhav and colleagues at Johns Hopkins University’s Mind/Brain Institute and Department of Mechanical Engineering. It’s an immersive virtual reality system that allows rats to experience a simulated world. True to its name, the Dome is a planetarium-like apparatus with a large fibreglass shell covering a running track. A projector mounted above the shell projects an image onto a mirror, which reflects it onto the inside surface of the Dome. This allows rats to move freely while traversing virtual space.
But why are we putting rats into advanced virtual reality environments?
The answer is related to, albeit indirectly, your commute home. Understanding where we are and how to get to our destinations is crucial for survival for all mobile organisms, including humans.
A breakthrough in understanding the neural basis of navigation came in the early 1970s with the discovery of place cells. Located in the hippocampus, these neurons fire whenever an animal is in a particular part of its environment. Place cells are influenced by various factors, including landmarks, borders, direction, smell, sound, speed and more.
The Dome takes advantage of this by allowing researchers to project various shapes—such as a slice of cheese— inside the surface of the Dome as landmarks. These landmarks can move at different speeds and directions and their motion is dependent on the rat’s own movements. This creates an augmented reality environment where the rat believes it is running slower or faster than it actually is. When the rat perceives it has completed a lap, informed by the landmarks, place cells fire.
By changing what the rat sees and hears, researchers can explore how altering sensory environments affects the firing patterns of place cells. This work deepens our understanding of the neural processes underlying navigation.
The hippocampus: more than just spatial information?
The hippocampus is classically thought of as the site for representing the spatial location of an animal – where it is and what its surroundings look like. However, recent studies suggest it can also encode non-spatial information—especially if that information is associated with a reward. Skylar’s project tests this idea.
“We wanted to see if the rats focus more on the information that’s more reward-relevant to them when exposed to multiple types of information,” Skylar explains. “Part of our experiments explore whether the hippocampus can encode sound if it is associated with reward when the rat is freely navigating in the Dome.”
These experiments make good use of the Dome’s speaker. Using the Dome’s speaker system, researchers play a constant tone that changes in pitch depending on the rat’s movement, creating a “sound frame.” The sound and landmark frames move at different “gains” relative to the rat’s movement, leading to conflict in the senses. Certain degrees within the sound frame are reward zones, where rats can take sips of sweet chocolate milk. In this setup, the landmark position and movement are irrelevant to reward.
Skylar hypothesized that the hippocampus prioritized task-relevant information. That is, the allure of a chocolate treat might entice rats to focus more on the soundscape rather than spatial cues.
Preliminary data supports this hypothesis. It suggests that CA1 neurons— a key group of hippocampal cells involved in memory and navigation— can encode the task-relevant sound frame. It seems like the hippocampus can encode more than just space when an animal experiences conflicting information!
The importance of foundational research
The hippocampus in humans is not only fundamental to spatial navigation, but it is also heavily involved in forming memories about our day-to-day experiences. Because spatial disorientation and loss of memory are some of the earliest symptoms of Alzheimer disease, this type of research is essential for understanding the brain and disease.
“If we don’t understand the basics of what is happening in the brain, our hands are tied,” Skylar says. “It might be difficult to figure out what went wrong in the diseased brain, and that really impacts our ability to help patients. Foundational research is the basis for continued research into neurological diseases.”
