Fenna Krienen, Ph.D., assistant professor at the Princeton Neuroscience Institute, has received a prestigious award from the NIH to study the outsized development of the neocortex in humans, the part of brain thought responsible for advance cognitive abilities, such as language, problem-solving, and empathy. Human’s expanded neocortex, while linked to enhanced cognition, is also highly susceptible to neurological disorders like autism and Alzheimer’s disease. As such, results from Krienen’s research may ultimately improve our understanding of brain health in the future.

The $2.4M NIH Director’s New Innovator Award, which supports innovative high-risk, high-reward research by early career researchers, will fund Krienen’s work to over the next five years. 

“The High-Risk, High-Reward program champions exceptionally bold and innovative science that pushes the boundaries of biomedical and behavioral research,” said Tara A. Schwetz, Ph.D., NIH Deputy Director for Program Coordination, Planning, and Strategic Initiatives and Director of the Division of Program Coordination, Planning, and Strategic Initiatives, which oversees the NIH Common Fund. “The groundbreaking science pursued by these researchers is poised to have a broad impact on human health.”

Human intelligence owes a debt of gratitude to the thin, wrinkled sheet of cells that form the brain’s outermost layer, the neocortex. 

The neocortex, the brain’s most recently evolved region, is thought to be responsible for many of the advanced cognitive abilities humans have evolved, such as complex language, spatial reasoning, and social behavior. Despite the souped-up neocortex, though, most mammals, including mice with brains 1000 times smaller than humans, all share a mostly similar blueprint for brain development.

“Mammalian brains develop and are structured according to a common plan,” Krienen said. “The basic layout of the brain is always the same, but then there are certain parts of the human brain, like the neocortex, that have expanded disproportionately and have acquired new forms of connectivity.”

To understand how humans and other primates struck neuronal gold compared to animals with a relatively smaller neocortex, like mice, Krienen and her team will use the award to trace the cellular identity of nerve cells across development.

In doing so, Krienen hopes to better understand how and when expanded brain regions like the neocortex emerge and diverge from cells that form more conserved areas across mammals.

“We use a virus that deposits a kind of breadcrumb in stem cells over each round of cell division,” Krienen said. “After the stem cells develop into neurons and settle into their final location as brain regions mature into their final forms, we can reconstruct the life history of that cell by sequencing the breadcrumbs deposited in its genome. That would enable me to tell you whether a cell in your prefrontal cortex is or isn’t developmentally related to a cell in your say, your motor cortex.”

Krienen joined the Princeton Neuroscience Institute in 2022. Before coming to Princeton, Krienen earned her Ph.D. in psychology at Harvard University in the lab of Randy Buckner, Ph.D., and completed her postdoctoral research in the lab of Steve McCarrol, Ph.D. in the department of genetics at Harvard Medical School and the Stanley Center for Psychiatric Research at the Broad Institute.