Mount Sinai neuroscientist sheds light on how the brain stores memories across a lifetime

Denise Cai, PhD, an Assistant Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai, has always been interested in the dynamic nature of memory. But she began to question precisely how the brain can store and recall so many memories over a lifetime while playing a "memory match" card game with her young son. While being beaten time and again, she began to wonder whether he could distinguish the cards and remember their locations so much better because his younger brain simply had more available "real estate" to form new memories.

Now, thanks to a major grant from the National Institutes of Health, she'll have the opportunity to explore this question in her lab. On Tuesday, October 1, 2019, the National Institutes of Health announced that Dr. Cai is the winner of a 2019 New Innovator Award. The grant provides $2.5 million over the next five years to support investigation into the ways the brain optimizes its capacity and efficiency for memory storage.

The New Innovator award is part of the NIH's High-Risk, High Reward Research program, which was created to accelerate the pace of biomedical, behavioral, and social science discoveries by supporting exceptionally creative scientists with high-impact ideas that may be too risky or at a stage too early to fare well in the traditional peer review process. The award specifically supports early-career investigators who are within 10 years of their final degree or clinical residency and have not yet received a research project grant or equivalent NIH grant.

While Dr. Cai has always been interested in memory, curiosity about how her son's brain was beating her brain sparked a new line of scientific inquiry. To succeed in the matching card game, the player has to remember each distinct card, as well as its location, and the distinctions are subtle (for example: Nemo the clownfish looking right; Nemo the clownfish looking left).

When my son Caiden kept beating me, I began to wonder if the way his brain was encoding memory of each new card was different than the strategy my older brain relied on. I hypothesized that a younger brain may experience less 'interference' from the a lifetime of old memories and that perhaps the classic understanding of how memories are encoded in the brain-;thought to be one independently on top of the other-;might only tell half the story. I further hypothesized that perhaps, as demand increases and we have more experiences to remember, the populations of neurons that encode these memories become increasingly interconnected.

Denise Cai, PhD, Assistant Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai

Through the support of the New Innovator Award funding, Dr. Cai will use a combination of innovative approaches to test these ideas. To record the neural activity in the brains of both younger and older mice as they learn new spatial locations, she will use a novel, wire-free miniature microscope, called the Miniscope system, which was co-developed with colleagues at the University of California, Los Angeles (UCLA) and the Icahn School of Medicine at Mount Sinai. Using this new technology, study mice will wear tiny, head-mounted, wire-free microscopes as they enter a variety of different environments, enabling researchers to record and analyze thousands of neurons over the course time.

"We will use a variety of techniques to observe and manipulate these populations of neurons to determine how the neural activity in the brain controls the animals' behavior," explains Dr. Cai. "Ultimately, we hope to learn how the brain optimizes its capacity to store information across a lifetime. I am tremendously grateful to have received the New Innovator Award, which will enable our lab to explore some fundamental, yet very complex, biological questions in the field of memory and cognition."

"Each year, I look forward to seeing the creative approaches these researchers take to solve tough problems in biomedical and behavioral research," said NIH Director Francis S. Collins, M.D., Ph.D. "I am confident the 2019 cohort of awardees has the potential to advance our mission of enhancing health through their groundbreaking studies."

Dr. Cai, who came to Mount Sinai from UCLA two years ago, has also recently received a 2019 One Mind Rising Star Award, which identifies and funds pivotal, innovative research on the causes of and cures for brain disorders by supporting the most promising emerging leaders in the field of neuropsychiatry. The $250,000 award will support her lab's research on the ways in which traumatic memories may be linked in the brain to "neutral" ones in such disorders as post-traumatic stress disorder.