In 2003, Chiara Cirelli from the University of Wisconsin-Madison theorized that this mass downscaling happens specifically while we sleep. In fact, she argued, it might be one of the reasons that sleep exists at all—to provide a quiet time when our brains can effectively renormalize our synapses, ready for another day of learning. That may partly explain why sleep is so universal among animals, and why our mental abilities take a hit after a sleepless night. Sleep is the price we pay for the ability to learn, and it’s non-negotiable.
Now, working independently, Cirelli and Huganir have both found support for this idea.
Cirelli’s team collected the brains of mice that were either awake or asleep, and used a powerful microscope to measure the size of almost 7,000 synapses. “It took four years, with around six people working manually,” she says. Chief among them was Luisa de Vivo, who found that, on average, synapses seem to shrink during sleep. Specifically, the contact area where the two neurons meet is 18 to 20 percent smaller in sleeping animals, compared to waking ones—a clear sign that they had weakened. And as predicted, they shrank by roughly the same proportion, maintaining their relative strengths.
While Cirelli’s team was focusing on the physical size of sleeping synapses, Huganir’s group looked at their chemistry. Specifically, he looked at receptor proteins—little docking stations, found at synapses, which allow neurons to receive chemical messages from their neighbors. The levels of these receptors, and particularly a class known as AMPA receptors, are a good indicator of a synapse’s strength. And that strength, as team member Graham Diering showed, falls during sleep.
He isolated large numbers of synapses from the brains of mice, both asleep and awake, and measured the levels of thousands of proteins. He also tagged some receptors with fluorescent molecules, and used a microscope to track them in the brains of living rodents. Both techniques revealed that many receptors, AMPA ones included, move away from the synapse while the mice snooze. “The composition of the synapse is really totally changing from wake to sleep,” says Huganir.
But #notallsynapses. Based on her data, De Vivo calculated that around 20 percent of the synapses—the largest ones, and therefore the strongest—were unaffected by this downscaling. And it’s not clear what that means. “Our interpretation is that the largest synapses are those that have been there for a long time,” says Cirelli. “They may be the repositories of very strong memories—like the name of your mum—which you’re very unlikely to forget, even if you’re sleep-deprived. The majority of synapses, which are scaled down, may be the ones more engaged in what happened recently. If they’re not linked to anything relevant over a few days, they disappear. That’d be my guess.”