Pupil changes play key role in memory formation

Cornell University researchers have found the pupil is key to understanding how, and when, the brain forms strong, long-lasting memories.

By studying mice equipped with brain electrodes and tiny eye-tracking cameras, the researchers determined that new memories are being replayed and consolidated when the pupil is contracted during a substage of non-REM sleep. When the pupil is dilated, the process repeats for older memories. The brain's ability to separate these two substages of sleep with a previously unknown micro-structure is what prevents "catastrophic forgetting" in which the consolidation of one memory wipes out another one.

The findings could lead to better memory enhancement techniques for humans and may help computer scientists train artificial neural networks to be more efficient. The study, under embargo until 11am ET on Jan. 1 in Nature, was led by assistant professors Azahara Oliva and Antonio Fernandez-Ruiz.

Over the course of a month, a group of mice was taught a variety of tasks, such as collecting water or cookie rewards in a maze. Then the mice were outfitted with brain electrodes and tiny spy cameras that hung in front of their eyes to track their pupil dynamics. One day, the mice learned a new task and when they fell asleep, the electrodes captured their neural activity and the cameras recorded the changes to their pupils.

Non-REM sleep is when the actual memory consolidation happens, and these moments are very, very short periods of time undetectable by humans, like 100 milliseconds. How does the brain distribute these screenings of memory that are very fast and very short throughout the overall night? And how does that separate the new knowledge coming in, in a way that it doesn't interfere with old knowledge that we already have in our minds?"

Azahara Oliva, Assistant Professor, Cornell University

The recordings showed that the temporal structure of sleeping mice is more varied, and more akin to the sleep stages in humans, than previously thought. By interrupting the mice's sleep at different moments and later testing how well they recalled their learned tasks, the researchers were able to parse the processes. When a mouse enters a substage of non-REM sleep, its pupil shrinks, and it's here the recently learned tasks – i.e., the new memories – are being reactivated and consolidated while previous knowledge is not. Conversely, older memories are replayed and integrated when the pupil is dilated.

"It's like new learning, old knowledge, new learning, old knowledge, and that is fluctuating slowly throughout the sleep," Oliva said. "We are proposing that the brain has this intermediate timescale that separates the new learning from the old knowledge."

The research was supported by the National Institutes of Health, the Sloan Foundation, the Whitehall Foundation, the Klingenstein-Simons Fellowship Program, and the Klarman Fellowships Program.