The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study

J Neurosci. 2013 Mar 6;33(10):4494-504. doi: 10.1523/JNEUROSCI.3127-12.2013.


An important function of sleep is the consolidation of memories, and features of sleep, such as rapid eye movement (REM) or sleep spindles, have been shown to correlate with improvements in discrete memory domains. Because of the methodological difficulties in modulating sleep, however, a causal link between specific sleep features and human memory consolidation is lacking. Here, we experimentally manipulated specific sleep features during a daytime nap via direct pharmacological intervention. Using zolpidem (Ambien), a short-acting GABAA agonist hypnotic, we show increased sleep spindle density and decreased REM sleep compared with placebo and sodium oxybate (Xyrem). Naps with increased spindles produced significantly better verbal memory and significantly worse perceptual learning but did not affect motor learning. The experimental spindles were similar to control spindles in amplitude and frequency, suggesting that the experimental intervention enhanced normal sleep processes. Furthermore, using statistical methods, we demonstrate for the first time a critical role of spindles in human hippocampal memory performance. The gains in memory consolidation exceed sleep-alone or control conditions and demonstrate the potential for targeted, exceptional memory enhancement in healthy adults with pharmacologically modified sleep.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Brain Waves / drug effects
  • Brain Waves / physiology*
  • Cross-Over Studies
  • Disorders of Excessive Somnolence / chemically induced
  • Disorders of Excessive Somnolence / physiopathology
  • Double-Blind Method
  • Electrocardiography
  • Electroencephalography
  • Electromyography
  • Female
  • Fourier Analysis
  • GABA-A Receptor Agonists / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Humans
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Movement / drug effects
  • Movement / physiology
  • Neuropsychological Tests
  • Polysomnography
  • Pyridines / pharmacology
  • Reaction Time / drug effects
  • Sleep Stages / drug effects
  • Sleep Stages / physiology*
  • Verbal Learning / drug effects
  • Verbal Learning / physiology
  • Young Adult
  • Zolpidem


  • GABA-A Receptor Agonists
  • Pyridines
  • Zolpidem