Sleepless Mice Have Memory Protected

University of Pennsylvania. Cells in a mouse hippocampus glow green when they have taken up a receptor that can overcome sleep deprivation.

While sleep deprivation can have similar effects to the less pleasant aspects of being drunkdiminishing sleep rates get only a fraction of the public attention of alcohol or drugs.

In 2009, Professor Ted Abel of the University of Pennsylvania demonstrated that the cyclic AMP (cAMP) signaling pathway is both important for memory formation and affected by lack of sleep. This year a paper from a different team revealed how sleep enables mice to grow dendritic branches associated with learning new tasks. When kept awake for too long, the mouse brains couldn't form the neurons needed to hold onto the skills they had been taught. 

In the Journal of Neuroscience, Robert Havekes, working in Abel's lab, identified the specific brain region affected by sleep deprivation. "The challenge following [our] study," Abel said, "was to determine if the impact of sleep deprivation was mediated by particular regions of the brain and particular neural circuits. We suspected that the hippocampus, the brain region that mediates spatial navigation and contextual memory, was critical."  

The protein octopamine causes the cAMP pathway to activate in fruit flies, but mice don't naturally respond to it. By placing a receptor for the protein in the brains of mice and then injecting the mice with octopamine, Havekes was able to determine where the receptor was expressed, and raise cAMP levels in those parts of the brain.

After preparing the mice in this way, the team trained the mice in a spatial memory task to find objects in a box. Once they learned the task, the scientists injected the mice with octopamine immediately after training as well as three hours later—two time windows that are associated with cAMP signaling contribution to memory consolidation. Some of the mice were allowed to sleep afterward, while others were repeatedly woken up.

The next day the mice were tested again with two objects in the same spot and one having been moved. "If the mice had learned and remembered the location of the objects during their training, then they would realize, okay, this is the object that has moved, and they'll spend more time exploring that particular object," Havekes explained. "If they didn't remember well, they would explore all the objects in a random fashion." 

Mice that had a good day's sleep or had been given octopamine spent extra time becoming familiar with the moved object, indicating their memories of its old location were strong. Those with neither sleep nor the receptor treated each object equally, clearly having forgotten where they used to be. By observing where the receptor was triggered, Havekes said “what we’ve shown is this memory loss due to sleep deprivation is really dependent on misregulation of cAMP signaling in the excitatory neurons of the hippocampus.”

However, before sleep deprived students get too excited, a memory pill is still a long way off. To get the receptor into the mouse neurons Havekes used a viral carrier, which might be a step too far for even the most exhausted student.

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