Sleep Deprivation within Five Hours of Learning Impairs Memory Consolidation in Mice

Tuesday, July 8, 2003

PHILADELPHIA -- Scientists at the University of Pennsylvania have found new support for the age-old advice to "sleep on it."  Mice allowed to sleep after being trained remembered what they had learned far better than those deprived of sleep for several hours afterward.

The researchers also determined that the five hours following learning are crucial for memory consolidation; mice deprived of sleep five to 10 hours after learning a task showed no memory impairment.  The results are reported in the May/June issue of the journal Learning & Memory.

"Memory consolidation happens over a period of hours after training for a task, and certain cellular processes have to occur at precise times," said senior author Ted Abel, assistant professor of biology at Penn.  "We set out to pinpoint the specific window of time and area of the brain that are sensitive to sleep deprivation after learning."  

Abel and his colleagues found that sleep deprivation zero to five hours after learning appeared to impair spatial orientation and recognition of physical surroundings, known as contextual memory.  Recollection of specific facts or events, known as cued memory, was not affected.  Because the brain's hippocampus is key to contextual memory but not cued memory, the findings provide new evidence that sleep helps regulate neuronal function in the hippocampus.

Abel's group studied fear conditioning in mice.  Animals received a mild electric shock in conjunction with one of two different types of stimuli.  Some mice were placed in a distinctive setting before receiving a shock, generating fear of that particular location.  Others heard a tone shortly before a shock was administered, causing them to fear the tone.

Abel assessed the permanence of this fear conditioning by observing how frequently the mice froze -- remaining completely motionless for a number of seconds -- when exposed 24 hours later to the cue associated with the shock.  Even when deprived of sleep, mice exposed to the audible tone remained fearful the following day.  

But mice that had learned to associate a general physical environment with administration of an electric shock were less likely to do so after sleep deprivation.  Sleep-deprived mice spent just 4 percent of their time frozen when returned to this environment the following day, compared to 15 percent among mice whose sleep was not disrupted in the five hours immediately after shock administration.

"It has been suggested that sleep serves a variety of physiological functions, ranging from energy conservation to refreshing the immune system," Abel said.  "Another important hypothesis is that sleep regulates neuronal function during memory consolidation.  Our findings provide support for this theory, and, by implicating hippocampal-dependent tasks during a specific time window, we have taken an initial step in clarifying the neural effects of sleep deprivation."

Abel's co-authors are Laurel A. Graves and Allan I. Pack of Penn's School of Medicine and Penn undergraduate Elizabeth A. Heller.  The work was supported by the National Institutes of Health, the Whitehall Foundation, the University of Pennsylvania Research Foundation and the Mental Retardation and Developmental Disabilities Research Center at Children's Hospital of Philadelphia.