Medical Examiner

Into the Cranium

This is the fourth installment of a five-part series.

Marcos Frank’s lab at the University of Pennsylvania is set up to eavesdrop on the neurons of young kittens, ferrets, and rats. In one room, an air table (a platform that can be suspended on a cushion of air) provides a vibration-free surface on which to perform surgery, cutting tiny holes in the animals’ craniums to expose a portion of their brains. (He uses anesthesia, and the animals don’t suffer.) Surrounding the table are surgical probes in Tupperware containers, catheters, gas valves, amplifiers, modified cameras, and an unreasonable thicket of cables—high-tech gear bound up with a rubber band.

When I arrive, Frank, wearing a tan ski cap and jeans, is reassembling a camera. Standing amid its parts, he explains that much of his work is aimed at deciphering how sleep alters brain circuitry, down to the level of individual neurons. In a typical experiment, he modifies the visual inputs that a group of developing animals receive, then allows some animals to sleep while others are kept awake in the dark. Later, he tries to pinpoint minuscule differences in how the animals’ brain cells are firing, in response to visual patterns on a screen. This means performing surgery to expose a group of brain cells, then suspending electrodes over particular cells to listen in. “It’s like dropping a microphone into a crowd of people, so that you’re above one person and listening to what they’re saying—although we don’t actually know the language,” he says.

Frank is an important mediator—and incisive critic—in the debate about sleep and memory. He argues that behavioral researchers  are in danger of hitting a “dead end” with contradictory findings on which parts of sleep enhance what kinds of memories. But he also finds fault with cell-level work that associates sleep with a particular molecular or genetic effect but doesn’t show how that matters for the animal.

We don’t know what the ultimate function of sleep is, Frank says. But many lines of converging evidence now support the idea that sleep promotes brain plasticity—that is, it reinforces changes in the brain brought about by waking experience.

In a set of experiments published in 2001, Frank demonstrated that sleep buttresses changes in the visual cortexes of newborn cats, which in turn change how the cats see. Neuroscientists have long known that if you take a young kitten and block one of its eyes, its brain will beef up the wiring that responds to the open eye. Frank demonstrated that in 1-month-old kittens, sleep heightens this experience. Plasticity can be thought of as a “cellular correlate of memory,” he says. In other words, sleep strengthened the cats’ neuronal “memory” of having an eye patched. (Since then, Frank has found that neurons need to “talk in their sleep”—that is, they need to be active—for this enhancement to occur.)

Frank’s work is impressive. And there is some evidence that the plasticity he observes in the visual systems of baby cats applies to other parts of the brain. Sleep probably has something to do with plasticity throughout life, but its precise role may change as baby brains grow up. There is speculation that early on, REM serves in part as a substitute for external experience, creating a kind of internal sound and light show that helps to ready the brain for experience and set up the foundations of some circuitry. But neuronal wiring is better established in adults, and we may not need this sort of stimulation. Adults spend proportionally less time in REM than babies do. So, perhaps as we age, we simply need less of whatever REM does for the brain during development. Or perhaps sleep serves to promote different kinds of plastic changes in adults—which we also get from non-REM sleep, which increases in adults.