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Priya Rajasethupathy: Memories mark DNA

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Priya Rajasethupathy: Memories mark DNA

Neuroscientist probes the memories of sea slugs and mice

Erin Wayman

10:57am, September 22, 2015

Priya Rajasethupathy has found a tiny molecule that may turn off part of the genome to allow the brain to store long-term memories.


Priya Rajasethupathy’s research has been called groundbreaking, compelling and beautifully executed. It’s also memorable.
Rajasethupathy, a neuroscientist at Stanford University, investigates how the brain remembers. Her work probes the molecular machinery that governs memories. Her most startling — and controversial — finding: Enduring memories may leave lasting marks on DNA.
Being a scientist wasn’t her first career choice. Although Rajasethupathy inherited a love of computation from her computer scientist dad, she enrolled in Cornell University as a pre-med student. After graduating in three years, she took a year off to volunteer in India, helping people with mental illness.
During that year she also did neuroscience research at the National Centre for Biological Sciences in Bangalore. While there, she began to wonder whether microRNAs, tiny molecules that put protein production on pause, could play a role in regulating memory.
SLUGGISH By observing nerve cells (shown) in sea slugs, Priya Rajasethupathy discovered small RNAs play a role in memory.">
SLUGGISH By observing nerve cells (shown) in sea slugs, Priya Rajasethupathy discovered small RNAs play a role in memory. P. Rajasethupathy
She pursued that question as an M.D. and Ph.D. student at Columbia University (while intending, at least initially, to become a physician). She found some answers in the California sea slug (Aplysia californica). In 2009, she and colleagues discovered a microRNA in the slug’s nerve cells that helps orchestrate the formation of memories that linger for at least 48 hours.
An even more intriguing finding in the sea slug’s nerve cells was piRNA, a molecule a bit bigger than a microRNA. In the presence of serotonin, a chemical messenger involved in learning, the piRNA suppresses production of a protein that hinders memory formation. Rajasethupathy and colleagues propose that the piRNA accomplishes this shutdown by indirectly altering the nerve cell’s genetic instructions. By adding chemical tags to DNA, the piRNA may turn off part of the genome — and keep it off for years. This sort of epigenetic change, Rajasethupathy says, “could be a mechanism for the maintenance of really long-term memories.”
Since arriving at Stanford in 2013, Rajasethupathy has begun working with mice, exploring neural circuits involved in memory retrieval. She’s also looking for links between abnormal memory behavior and particular genetic mutations, with the goal of determining how those genetic changes might disrupt neural circuitry. Such findings could provide insights into neurological disorders, she says.

Although she dropped her medical ambitions, Rajasethupathy says her clinical training is an asset. “Having the medical perspective broadens the scope and questions that you can think about.”

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