The Science of Sleep

“There’s this view that sleep is for the weak,” says Ted Abel. “‘I’m getting ready for final exams, I’m just gonna stay up, I’ll be fine.’” Not so fast: New research from Abel’s lab has illuminated the specific molecular mechanism in mice of how sleep deprivation can sap the ability to remember things. Though it may someday reveal ways to reverse some of those effects, for now, Abel says, the work makes an important and immediate point.

“We don’t have a magic pill to take to fix this, but what I think we can admit as a society, as a culture, is that sleep is a biological necessity, and taking time for that should be a priority.” Abel, the Brush Family Professor of Biology and co-director of the Biological Basis of Behavior Program, published the work with lead author and senior research associate Robbert Havekes, others in Abel’s lab, and collaborators in the Netherlands and Germany, in the Journal of Neuroscience. They found that a molecule known as cyclic AMP, or cAMP, is responsible for mediating memory loss in mice in a brain region called the hippocampus.

The hippocampus is known to play a big role in memory in humans as well. Episodic memory in particular is controlled there, meaning our memories of people, places, things, and events. “Memory for what occurs when,” Abel says.

Havekes set up an experiment using mice to test memory and sleep loss within the hippocampus. He used what is known as a pharmacogenetic approach: The mice were engineered to express a receptor in certain cells within the hippocampus that was essentially “silent” until a particular agent was injected. The agent was octopamine, a neurotransmitter found naturally in invertebrates but not in mice. When octopamine is introduced into the modified mouse brains, cyclic AMP levels are increased. This, they found, had a large effect on memory.

Of course, we can’t ask mice to take a final exam to see what they remember from their night of cramming. To test their memory, the researchers introduced three objects into the mouse environment, and the rodents were allowed to explore. Later, they explored again after one of the objects had been moved. Mice with intact memories will explore the moved object more, indicating they remember the objects’ positions and are investigating this “new” object in more detail. Sleep-deprived mice, meanwhile, explore all three equally; they don’t remember enough to know that one had been moved.

Enter the octopamine: mice injected with this agent, and thus with elevated cAMP levels, do remember that one object seems to be in a different place, even if they are suffering from sleep deprivation. Increasing cAMP essentially removed the negative effects of sleep loss on memory.