From learning a new instrument to mastering a new sport, the human brain is constantly reshaping itself in response to experience. This ability—known as brain plasticity—is essential for development, learning, and adaptation throughout life. UT neuroscientist Keerthi Krishnan is working to understand what happens when that process goes awry and how insights at the genetic and cellular level could inform treatments for neurological disorders.
Krishnan, an associate professor of biochemistry and cellular and molecular biology in the College of Arts and Sciences and the director of NeuroNet—a UT-led interdisciplinary brain research center—studies how genes influence the brain’s capacity to change. Her research spans development and adulthood, health and disease, and sits at the intersection of genetics, behavior, and neural circuitry.
“At its core, my work asks how experience shapes the brain,” Krishnan said. “We know that when we learn something new—whether it’s walking, talking, or picking up a skill—the brain physically changes. The question is what mechanisms allow that to happen, and what breaks down in neurological disorders.”
When communication and experience fall out of sync
A central theme of Krishnan’s work is the idea that some neurodevelopmental disorders arise from a lack of communication between the brain’s internal wiring and the external environment. One disorder that illustrates this disconnect is Rett syndrome, an autism-associated neurological condition in which early development often appears typical but is followed by a period of regression in which previously acquired skills are lost.
“In conditions like Rett syndrome, the brain is largely intact,” Krishnan said. “The question is why the cells aren’t communicating in a coordinated way and how that lack of coordination affects behavior.”
The syndrome is caused by mutations in the gene MECP2, often referred to as a “master regulator” gene because it binds to DNA and influences the activity of thousands of other genes. Despite decades of study, scientists are still working to fully understand why disruptions in the MECP2 gene lead to widespread effects on brain function and behavior.
Krishnan’s lab approaches the problem by examining how genetic disruptions influence cellular function, neural networks, and behavior across the brain, offering a more integrated view of how the disorder unfolds.
How cellular diversity contributes to behavior
To study brain plasticity, Krishnan’s team uses a wide array of tools including genome-wide profiling of gene expression, high-resolution imaging, electrophysiology, and behavioral analysis in animal models. A focus of her lab is understanding how specific cell types contribute to learning and to motor skills such as the fine control involved in reach-to-grasp movements.
“One of the challenges in neuroscience is cellular diversity,” Krishnan said. “The brain has thousands of distinct cell types. Understanding which cells matter for which behaviors—and how genes like MECP2 affect them—is incredibly complex.”
That complexity is amplified in many conditions, such as Rett syndrome, in which some cells express the mutated gene while others do not. Krishnan’s work suggests that the disorder is not caused simply by the loss of MECP2 in individual cells but by disrupted communication between cells that express the gene and those that do not.
“This shifts how we think about the disease,” she said. “It’s not just about replacing what’s missing. It’s about understanding how networks are formed and maintained and how imbalance affects the entire system.”
Timing, plasticity, and broader implications
Another key insight from Krishnan’s research on Rett syndrome is the importance of timing. Her work shows that the brain may compensate for genetic disruptions early in development only to lose that flexibility later in life.
“There are windows when the brain can adapt and maintain function,” she said. “Later, that ability seems to fade. Understanding why that happens—and whether we can extend or restore those windows—is one of the most exciting questions in the field.”
The findings have implications beyond Rett syndrome. MECP2 is active throughout the body and has been implicated in a range of conditions from cancer to schizophrenia. Studying how this gene works in both health and disease has the potential to reveal broader principles of brain regulation and resilience.
Machine learning and a systems-level view of the brain
To tackle the scale and complexity of modern neuroscience data, Krishnan’s lab is integrating advanced computing and machine learning approaches. Deep learning tools help the team quantify subtle behavioral patterns and connect them to cellular and molecular changes in the brain—analyses that were not possible just a few years ago.
“Neuroscience and computational science now go hand in hand,” Krishnan said. “We’re finally getting to the point where we can analyze whole-brain data and ask questions at a systems level.”
That interdisciplinary mindset is one reason UT is a strong environment for brain research. Collaborations across neuroscience, data science, engineering, and psychology are helping researchers address complex questions.
This systems-level approach extends beyond Krishnan’s own lab. As director of NeuroNet, a UT research center focused on bridging brain, cognition, and behavior, she helps connect researchers across disciplines and institutions to tackle complex questions about the brain. NeuroNet brings together faculty from 13 departments and four colleges along with collaborators at UT Medical Center and Oak Ridge National Laboratory, creating a collaborative environment where neuroscience intersects with engineering, data science, psychology, and medicine.
“No single lab or discipline can solve these problems alone,” Krishnan said. “The brain doesn’t operate in silos, and neither should neuroscience.”
Training the next generation
As Krishnan’s lab continues to explore how plasticity is established, maintained, and lost, the ultimate goal is to translate discoveries into meaningful improvements in quality of life.
“Understanding how the brain adapts—and why it sometimes can’t—has implications for learning, rehabilitation, and neurological disease,” she said. “If we can figure out how to preserve or restore plasticity, even partially, it could make a real difference.”