Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

Laboratory of Sleep and Cognitive Neuroscience, and Departments of Psychiatry and Neurology, Boston University School of Medicine, Boston, Massachusetts 02118.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 03/2013; 33(10):4561-9. DOI: 10.1523/JNEUROSCI.5525-12.2013
Source: PubMed


Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction.

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    • "REM sleep is characterized by fast, low-amplitude oscillatory activity in the θ-band (4–8 Hz) and higher frequency bands characteristic of waking (van der Helm et al., 2011). REM sleep also includes ponto-geniculo-occipital (PGO) waves that are intense bursts of synchronized activity propagating from the pontine region of the brain stem to the lateral geniculate nucleus and visual cortex (Datta and O’Malley, 2013). Behavioral hallmarks of REM sleep are phasic bouts of REM (hence the phase’s name) and muscle atonia (Jones, 1979). "
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    • "Effects of sleep on learned response inhibition have so far been mainly examined using fear extinction paradigms. The studies consistently showed a beneficial effect of sleep on fear extinction learning in rats and humans that was linked to both signs of NonREM sleep and REM sleep (e.g., Pace-Schott et al. 2012; Spoormaker et al. 2012; Kleim et al. 2013; Datta and O’Malley 2013; Fu et al. 2007; Silvestri 2005). Whereas the present study is limited in that it did not apply electrophysiological recordings to differentiate specific sleep stages, it adds to those previous observations in demonstrating a robust sleep benefit for learned response inhibition using an appetitive, rather than aversive, behavioral approach in which inhibitory memory might be differently mediated. "
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