A “golden age” for studying the brain | MIT News

As an undergraduate, Mitch Murdock was a rare science and humanities major, majoring in both English and molecular, cellular, and developmental biology at Yale University. Today, as a PhD student in MIT’s Department of Brain and Cognitive Sciences, he sees how his English education 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,” Murdock explains. “I was excited to try to bridge this gap between internal experiences of the world and this actual biological substrate of the brain.”

Although he can see those connections now, it wasn’t until 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 graduation as a research technician; 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 patterning of brain circuits.

It was in Liston’s lab that Murdock was first exposed to neuroscience and began to see the brain as the biological basis for the philosophical questions about experience and emotion that interested him. “It was really in his lab that I thought, ‘Wow, this is great.’ I have to get a PhD studying neuroscience,’” laughs Murdock.

During his time as a research technician, Murdock examined the impact of chronic stress on the brain activity of mice. Specifically, he was interested in ketamine, a fast-acting antidepressant prone to abuse, in the hope 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 memory storage. Their findings, Murdock explains, suggested that ketamine works by restoring dendritic spines that can be lost after periods of chronic stress.

After three years at Weill Cornell, Murdock decided to pursue doctoral studies in neuroscience, hoping to continue some of the work he began with Liston. He chose MIT because of the research being done on dendritic spines in the lab of Elly Nedivi, the 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 wider set of interests led Murdock to a new passion. During lab rotations early in his doctoral program, Murdock spent time shadowing a physician at Massachusetts General Hospital who was working with patients with Alzheimer’s disease.

“Everyone knows that Alzheimer’s has no cure. But I realized that, really, if you have Alzheimer’s disease, there’s very little you can do,” 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. Over the past five years, Murdock has worked with Tsai on several lines of Alzheimer’s research.

In one project, for example, members of the Tsai lab have shown how certain types of noninvasive light and sound stimulation induce brain activity that can improve memory loss in mouse models of Alzheimer’s. Scientists think that during sleep, tiny movements of blood vessels drive spinal fluid into the brain, which in turn removes toxic metabolic waste. Murdock’s research suggests that certain types of stimulation can trigger a similar process, removing debris that can exacerbate memory loss.

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

To answer these questions, Murdock relies on new single-cell sequencing techniques that he says have changed the way we think about the brain. “This has been a major breakthrough for the field, because we know that there are many different types of cells in the brain and we think they may contribute differently to the risk of Alzheimer’s disease,” says Murdock. “We can’t think of the brain as just about neurons.”

Murdock says this kind of “big picture” approach—thinking of the brain as a collection of many different types of cells that are interacting—is the central tenet of his research. To look at the brain in the kind of detail this approach requires, Murdock is working with Ed Boyden, the Y. Eva Tan Professor of Neurotechnology, MIT Professor of Biological Engineering and Brain and Cognitive Sciences, Howard Hughes Medical Institute Investigator and a member of the McGovern Institute for Brain Research at MIT and the Koch Institute for Integrative Cancer Research. Working with Boyden has allowed Murdock to use new technologies such as expansion microscopy and genetically encoded sensors to aid his research.

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

Right now, though, Murdock is focusing on a review article that synthesizes some of the latest research. Given the mountains of new Alzheimer’s work coming out each year, he admits that synthesizing all the data is a little “crazy,” but he couldn’t be happier to be in the middle of it. “There’s so much we’re learning about the brain with these new techniques, and it’s so exciting.”

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