Unravelling Memory’s Mysteries: A Profile of Elizabeth Buffalo
Unravelling Memory’s Mysteries: A Profile of Elizabeth Buffalo

Unravelling Memory’s Mysteries: A Profile of Elizabeth Buffalo

Studying nonhuman primates, the University of Washington neuroscientist has identified important features of the neural underpinnings of learning and memory.

Diana Kwon
Diana Kwon
May 1, 2020

ABOVE: BUFFALO LAB

As rodents scuttle through a maze, scientists can observe the activity of their brains’ “inner GPS,” neurons that manage spatial orientation and navigation. This positioning system was revealed through two different discoveries, decades apart. In 1971, neuroscientist John O’Keefe found place cells, neurons that are consistently activated when rats are in a specific location, while observing the animals as they ran around an enclosure. More than thirty years later, neuroscientists May-Britt and Edvard Moser used a similar method to identify grid cells, neurons that fire at regular intervals as animals move, enabling them to keep track of navigational cues.  

It was the early 2010s when neuroscientist Elizabeth Buffalo and her team at Emory University’s Yerkes National Primate Research Center in Atlanta started investigating what the brain’s GPS looks like in primates. While conducting memory tests by tracking the eye movements of primates viewing either familiar or unfamiliar images, the researchers began to wonder: Was this system also active in stationary animals? “They were moving their eyes as they were forming a memory of these pictures,” Buffalo says. “So we thought that maybe this eye movement exploration was something that primates do in an analogous way to how rodents explore as they move around a physical environment.”

 
Jill Riemer

One of Buffalo’s graduate students, Nathaniel Killian, put this hypothesis to the test. Working with monkeys, he placed electrodes into the entorhinal cortex—the brain region where grid cells are found in rodents—and recoded brain activity while the animals viewed images on a screen. One day, Killian came into a lab meeting with an announcement: he had found grid cells in the primate brain. Although it took many more months to complete additional experiments to validate the results, Buffalo remembers thinking during that meeting, “Wow, we’re seeing something really new.” 

From the basement to the lab bench

Buffalo conducted her first scientific experiment as a teenager in Little Rock, Arkansas. Encouraged by her high school science teacher, she embarked on an ambitious science fair project, which involved investigating the behavioral effects of a chemical called para-chlorophenylalanine (PCPA) on rats. Inspired by a TV news segment noting that extreme risk takers had increased aggressiveness associated with higher-than-average levels of PCPA, Buffalo decided to put the behavioral effects of the chemical to the test. 

To carry out the experiment, Buffalo set up a makeshift lab in the basement of her house. Her science teacher helped her gather the necessary materials and expertise by connecting her with a professor at the nearby University of Arkansas Medical School. That professor provided guidance for her project and got her in touch with the Arkansas-based National Center for Toxicological Research, which donated rats for her experiment. Buffalo housed the rodents in cages with water bottles provided by the university. She injected the animals with different concentrations of PCPA, then examined changes in aggression levels by administering a small electric foot shock and documenting how much of a small wooden rod the animals would chew away in response. As she’d hypothesized, higher doses of PCPA made the rodents more aggressive. “It ended up being a pretty involved project,” Buffalo recalls. “At one point, we had 20 rats in the basement.” 

Notable positions & awards

  • Professor, Physiology and Biophysics, University of Washington
  • Chief, Division of Neuroscience, Washington National Primate Research Center (2015–present)
  • Associate Professor of Neurology, Emory University School of Medicine (2012–2013)
  • Assistant Professor of Neurology, Emory University School of Medicine (2005–2012) 
  • McKnight Endowment Fund for Neuroscience Memory and Cognitive Disorders Award, 2018
  • National Academy of Sciences Troland Research Award, 2011

The experience solidified Buffalo’s interest in science and jumpstarted a series of summer jobs doing research. Most of those were spent in a behavioral toxicology lab led by Merle Paule at the National Center for Toxicological Research. Buffalo spent several summers during high school and college in Paule’s lab, working on experiments involving monkeys—such as assessing the behavioral effects of caffeine and other drugs on the animals. She coauthored a handful of papers about their research. 

Although Buffalo maintained an interest in science, she majored in philosophy at Wellesley College, where she started her undergraduate studies in 1988. She traces this decision back to a book, Scientific Realism and the Plasticity of Mind, by Canadian philosopher Paul Churchland, which she’d read while doing research for her high school science fair project. “I probably didn’t understand half of it, but it just was super interesting,” Buffalo says.

Greatest Hits

  • Found grid cells were active in the primate brain while a stationary animal is visually exploring a space
  • Identified differences in the synchronization of electrical signals across the layers of cortex within the neural circuit involved in processing attention
  • Revealed that visual memory and visual perception are processed in different regions of the brain

Although science wasn’t her major, the subject remained a dominant force in Buffalo’s life. Intrigued by the brain, she concentrated her studies on the philosophy of mind, choosing psychobiology, which dealt with the biological basis of psychological processes, as her minor. Buffalo’s first neuroscience professor, the late Howard Eichenbaum, sparked her interest in learning and memory. “He would get super excited and enthusiastic about what he was talking about,” Buffalo says. “I had these moments through almost every class where I thought, gosh, the most exciting thing I could ever try to figure out is exactly what happens in the brain when we learn something.” 

Philosophy meets neuroscience

After completing her undergraduate degree in 1992, Buffalo went to graduate school with the goal of becoming a philosophy professor. She enrolled in a doctoral program at the University of California, San Diego, to work with philosopher Patricia Churchland, wife of the very Paul Churchland who had authored the book that first piqued Buffalo’s interest in philosophy. “I was seeking out a philosopher who really cared about neuroscience,” Buffalo says. “She focused on philosophy of mind with the idea that, in order to really understand the mind, what we need to understand is the brain.”

Churchland led Buffalo on an interdisciplinary route, encouraging her to take classes with the neuroscience PhD students and to join a lab. Buffalo ended up in the joint lab of neuroscientists Larry Squire and Stuart Zola, two of Churchland’s colleagues who studied memory. “It became clear that [Buffalo] really loved this idea of neuroscience, and that she was bringing to neuroscience a kind of philosophical framework,” says Zola, who is now at the Yerkes National Primate Research Center. “She asked a lot of questions, making us think more about where we were headed and why, and how to interpret findings in ways that we might not have thought.” 

I had these moments through almost every class where I thought, gosh, the most exciting thing I could ever try to figure out is exactly what happens in the brain when we learn something.

—Elizabeth Buffalo, University of Washington

With Squire and Zola, Buffalo worked on identifying the borders between brain structures involved in memory, particularly episodic memories of everyday events and those associated with visual perception. Buffalo recalls wondering: “Is it just a continuum or is there really kind of this packaging, where you could say that one area really is involved in memory and the other area was involved in visual perception?”

By examining the behavior of human patients and monkeys with brain lesions, Buffalo and her colleagues found evidence for packaging. Through a series of investigations that involved going back to data from old experiments, they revealed that damage to the medial temporal lobe, a region that contains key memory-related structures such as the hippocampus, impaired memory, while injury to the adjacent anterior inferotemporal cortex led to deficits in visual perception but left memory intact. 

“She realized, I think, before many people did, that if you were going to understand what the heck the hippocampus did and what it really had to do with episodic memories, you need to understand the cortical structures that feed into the hippocampus,” Churchland says. 

Buffalo originally planned to obtain two doctorates—one in philosophy and the other in neuroscience. After completing her first dissertation in neuroscience, however, she decided she was eager to continue doing research. So in 1998 she left her philosophy PhD behind and headed east to start a postdoc with Robert Desimone, a neuroscientist who was then at the National Institute of Mental Health. Buffalo was drawn to Desimone’s lab because his group was investigating brain function at the level of individual cells rather than brain regions, which had been the focus of Zola and Squire’s lab. “What I was interested in at the time was how the activity of neurons would contribute to behavior,” Buffalo says. 

In Desimone’s lab, Buffalo examined neuronal activity in primates by recording both individual neurons and local field potential, electrical signals produced by groups of neurons. Using this method, Buffalo helped unveil important features of the neural circuitry of attention, which was the focus of Desimone’s team. Among other things, her work revealed that attention to a stimulus enhanced the synchronization of high-frequency signals in the superficial layers of a brain region called the visual cortex, while it reduced the synchronization of low-frequency signals in deeper layers of the same brain area. The result suggests the different patterns of synchronization across brain layers play an important role in how the signals are processed and sent onward in the brain. 

Five years into her postdoc, as her projects were beginning to wind down, Buffalo started to think about her options. “I really wanted to stay in academia, but I wasn’t convinced that I was going to be able to find a job,” Buffalo says. “It was, as it is now, a really hard time—and there were very few good tenure track jobs for primate neurophysiologists.” But just as Buffalo was considering making the switch to science policy or science writing, she got a call from Zola, her former PhD advisor. He had just been appointed the director of the Yerkes National Primate Research Center at Emory University and wanted to recruit Buffalo for an open faculty position. “Sometimes you just get really lucky,” Buffalo says. “It was a great environment, so I was really excited to have the chance to set up my lab.” 

Before getting that serendipitous call, Buffalo had applied at other universities. But there were personal reasons that went into her decision to accept Zola’s offer. “I won’t name names, but there were a couple of job interviews that I went on, where . . . [I got] the feeling that as soon as I said I had a female partner, the tone of the conversation really kind of changed,” she explains. “I decided early on that I’m not going to hide anything because I don’t want to move my family somewhere where it would be an issue. But I do think that has limited our choices.” 

Memories and moves

As Buffalo was building her lab at Emory, her wife was also starting a new job as director of a nonprofit organization in Atlanta, and the couple had a four-month-old son. “Thinking back, it was a crazy time,” Buffalo recalls. Luckily, even before she had finished setting up her lab, Buffalo already had a graduate student on board. Michael Jutras had done research on learning and memory in rodents as an undergraduate at Brown University, and was passionate about continuing his work on this topic. “He and I really built the lab together,” Buffalo says. 

She realized, I think, before many people did, that if you were going to understand what the heck the hippocampus did and what it really had to do with episodic memories, you need to understand the cortical structures that feed into the hippocampus.

 —Patricia Churchland, UCSD

Once her lab was ready, Buffalo immediately knew what experiments to pursue. She wanted to shift away from studying attention back to memory. During grad school, Buffalo had focused on examining the neural structures associated with memory. Now, she was equipped with the techniques she’d learned from Desimone’s lab to investigate brain waves and other physiological signatures of memory formation and retrieval. It was using these electrical recording tools that Buffalo and her team demonstrated the existence of grid cells in the primate brain. 

“She really is an exemplary mentor for graduate students and postdocs,” says Killian, who led the work on primate grid cells. “She created an environment where people were able to really conduct great science.” Buffalo was also thoughtful—each Christmas, she’d give every lab member a book “tailored to everyone’s unique interests,” Killian recalls. 

As the years passed, Buffalo was recruited to join other universities, so she and her family began to consider where else they might want to live. They liked Atlanta, but after careful consideration, they decided Seattle might be an ideal choice: Buffalo’s wife had family on the West Coast, and there was a primate center at the University of Washington (UW). When Buffalo reached out to the university to ask about open faculty positions, she was in luck: the chair of the physiology and biophysics department informed her that a search for a new faculty member would start in a couple of months and encouraged her to apply. She submitted an application and landed the job.

Buffalo moved her lab to UW in 2013 to continue her work on memory. Now, she and colleagues are using virtual reality to more closely investigate how place cells and grid cells are behaving in the primate brain. A burning question for her is how the brain’s representation of space aligns with its recollection of the time spent there, Buffalo says. “Why is it that we have these spatial representations right in the structure that we know is important for memory?”

Updated (May 5): Elizabeth Buffalo began looking for jobs five years into her postdoc, not eight years, as originally reported. The Scientist regrets the error.