Biology professor Matt Carter recently published groundbreaking research on the area of animals’ brains that communicate fullness during eating. As he travels the country presenting the findings, he says many of his colleagues are surprised by one detail: Carter’s research team is composed primarily of undergraduates.

Their work, which took place over the course of five years and involved 10 students, is now the subject of an article published in the journal eLife in May 2022. It is also poised to have a substantial impact on the field of neuroscience.

It began in 2017. Theresa Legan ’14 was using a method called retrograde tracing to examine a group of neurons called the parabrachial nucleus, which are known to suppress appetite. The psychology major, who joined the lab while working as an assistant softball coach at Williams, noticed a group of cells she couldn’t identify. Legan called Carter over to the microscope for help.

“I looked, and I had no idea what they were, either,” Carter says.

The pair checked databases and brain atlases and discovered that the cells came from a region called the parasubthalamic nucleus (PSTN).

“And it was an unknown brain structure,” Carter says.

“Not only is it rare for undergrad students to have access to the genetically encoded tools that were regularly used in [Carter’s] lab, but it is almost unheard of for them to have their very own projects. Working in the lab fundamentally changed my career path.” —Olivia Barnhill ’19, who worked in biology professor Matt Carter’s lab as a senior

Most brain regions have been the subject of thousands of studies each. But, at the time, only 20 articles had been published about the PSTN. And no one had attempted to stimulate or inhibit the neurons to gauge their effect on behavior. Carter had a new line of inquiry.

A senior in his lab, Jacob Sperber ’18, developed a series of tools to experiment on the PSTN. Next, senior Olivia Barnhill ’19 used the tools to conduct a full range of experiments showing that stimulating the cells suppressed appetite while inhibiting them increased food intake.

Barnhill, a psychology and biology major with a concentration in neuroscience, called her experience in Carter’s lab “incredibly formative” and says it “solidified my passion for neuroscience.” She is now working on her Ph.D. in the field at the University of California, San Francisco.

The team’s preliminary data led to a $369,000 National Institutes of Health grant in 2018. Carter used it to expand the team, hiring four students to conduct additional experiments into the effects of stimulating and inhibiting the cells. A final group of students conducted follow-up experiments and prepared the research, “A discrete parasubthalamic nucleus subpopulation plays a critical role in appetite suppression,” for publication in eLife.

Jessica Kim ’19, a psychology major who first joined the lab as a junior in 2017, stayed on as a technician after graduation. She continued her independent research project and took the helm as co-author of the article.

“I was incredibly lucky to take part in this level of research as an undergraduate,” says Kim, who is now in veterinary school at Midwestern University’s Arizona campus. “I was able to perform techniques that were often reserved for graduate students and postdocs.”

Carter calls the eLife article “a nice opus,” saying he enjoyed watching “a student start by reproducing what another student did the previous year but then take it forward.”

And there’s more for Carter’s lab to study, including how PSTN communicates with other brain regions and the full range of stimuli that activate the neurons.

“This is my favorite project I’ve ever worked on,” Carter says. “We were looking at an important brain region for the first time—studying something truly novel.”

• Spring 2017: Theresa Legan ’14 identified cells in the PSTN, which was largely unstudied. Carter invested resources to study them in more detail.
• 2017-18: Jacob Sperber ’18 developed tools to experiment on the PSTN and found some evidence that the neurons are active following a meal.
• 2018-19: Olivia Barnhill ’19 conducted a full range of experiments to study Tac 1, a cell subtype in the PSTN, and showed that stimulating these cells suppresses appetite while inhibiting these cells increases food intake.
• 2019-20: Lauren Heuer ’20 imaged cell populations and showed the PSTN can be divided into two subtypes, Tac1 cells and corticotropin-releasing hormone (CRH) cells. Grace Kromm ’20 stimulated Tac1 cells in freely moving mice and examined the effects on appetite suppression. Sierra Loomis ’20 stimulated CRH cells in freely moving mice. Matt Newman ’20 inhibited PSTN cells and showed that they are necessary for normal feeding and for the full effects of appetite-suppressing hormones from the digestive system.
• 2020-21: Jessica Kim ’19, Faris Gulamali ’21 and Kenny Han ’21 used fiber photometry to measure the activity of PSTN neurons in freely moving mice. Kate Jensen, assistant professor of physics, helped with the coding and data analysis required to interpret the results.

Kim Catley is a freelance writer based in Richmond, Va.

Above photo: Two types of cells are located in the parasubthalamic nucleus: appetite-suppressing Tac1 cells are shown in magenta, and CRH cells are shown in green. Photograph courtesy of Matt Carter.