A “golden era” to study the brain | MIT News

As an undergraduate, Mitch Murdock was a rare dual major science and humanities major, majoring in both English and molecular, cellular, and developmental biology at Yale University. Now a graduate student in MIT’s Department of Brain and Cognitive Sciences, he sees obvious ways in which his English education has broadened his horizons as a neuroscientist.

“One of my favorite parts of English was trying to explore interiority and how people have really complicated experiences inside their heads,” explains Murdock. “I was excited about trying to bridge this gap between inner experiences of the world and the brain’s actual biological substrate.”

Although he can now see these connections, it was only after Yale that Murdock became interested in brain science. As a student, he was in a traditional molecular biology lab. He even planned to stay there after graduating as a research engineer; Fortunately, however, he says his advisor Ron Breaker encouraged him to explore the field. That’s how Murdock ended up in a new lab led by Conor Liston, an associate professor at Weill Cornell Medicine who studies how factors like stress and sleep regulate the modeling of brain circuits.

It was in Liston’s lab that Murdock first encountered neuroscience and began to see the brain as the biological basis of the philosophical questions of experience and emotion that interested him. “It was really in his lab where I was like, ‘Wow, that’s so cool. I have to do a PhD in neuroscience,’” laughs Murdock.

During his time as a research technician, Murdock studied the effects of chronic stress on brain activity in mice. In particular, he became interested in ketamine, a fast-acting antidepressant prone to abuse, hoping that a better understanding of how ketamine works will help scientists find safer alternatives. He focused on dendritic spines, small organelles attached to neurons that help transmit electrical signals between neurons and provide the physical substrate for storing memories. His findings, Murdock explains, suggest that ketamine works by restoring dendritic spines, which can be lost after periods of chronic stress.

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After three years at Weill Cornell, Murdock decided to pursue a PhD in neuroscience in hopes of continuing some of the work he had started with Liston. He chose MIT because of the research on dendritic spines in the lab of Elly Nedivi, William R. (1964) and Linda R. Young Professor of Neuroscience at the Picower Institute for Learning and Memory.

Once again, however, the opportunity to explore a broader range of interests happened to lead Murdock to a new passion. During lab rotations early in his PhD program, Murdock spent some time mentoring a physician at Massachusetts General Hospital who worked with Alzheimer’s patients.

“Everyone knows that Alzheimer’s cannot be cured. But I realized that there’s really very little you can do when you have Alzheimer’s disease,” he says. “That was a big wake-up call for me.”

After this experience, Murdock strategically planned his remaining lab rotations, eventually settling in the lab of Li-Huei Tsai, the Picower Professor of Neuroscience and director of the Picower Institute. For the past five years, Murdock has worked with Tsai on various strands of Alzheimer’s research.

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For example, in one project, members of the Tsai lab have shown how certain types of non-invasive light and sound stimulation induce brain activity that can ameliorate memory loss in mouse models of Alzheimer’s disease. Scientists believe that small movements in blood vessels during sleep propel spinal fluid into the brain, which in turn flushes out toxic metabolic waste. Murdock’s research suggests that certain types of stimulation might drive a similar process, flushing out waste that can worsen memory loss.

Much of his work focuses on the activity of individual cells in the brain. Are certain neurons or neuron types genetically predisposed to degenerate, or are they destroyed randomly? Why do certain subtypes of cells appear to be dysfunctional earlier in the course of Alzheimer’s disease? How do changes in blood flow in vascular cells affect degeneration? All of these questions, Murdock believes, will help scientists better understand the causes of Alzheimer’s, which will eventually translate into the development of cures and therapies.

To answer these questions, Murdock is relying on new single-cell sequencing techniques that he says have changed the way we think about the brain. “This was a big step forward for the field because we know there are many different cell types in the brain and we think they may contribute differently to the risk of Alzheimer’s disease,” says Murdock. “We cannot think of the brain as just neurons.”

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Murdock says this kind of “big picture” approach – viewing the brain as an assemblage of many different cell types all interacting – is the central tenet of his research. To look at the brain in the level of detail that this approach requires, Murdock works with Ed Boyden, the Y. Eva Tan Professor of Neurotechnology, a professor of bioengineering and brain and cognitive sciences at MIT, a Howard Hughes Medical Institute investigator, and fellow the MIT McGovern Institute for Brain Research and the Koch Institute for Integrative Cancer Research. Working with Boyden has enabled Murdock to use new technologies such as expansion microscopy and genetically encoded sensors to aid in his research.

This kind of new technology, he adds, has helped open the field wide. “This is such a cool time to be a neuroscientist because the tools now available make this a golden era for studying the brain.” This rapid intellectual expansion also applies to the study of Alzheimer’s disease, including the newly understood connections between the immune system and Alzheimer’s disease – an area in which Murdock hopes to continue after graduating.

For now, however, Murdock is focused on a review paper summarizing some of the latest research. With mountains of new Alzheimer’s papers coming out each year, he admits that synthesizing all the data is a bit “crazy,” but he couldn’t be happier to be right in the middle. “We’re just learning so much about the brain through these new techniques, and it’s just so exciting.”

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