Infralimbic activity during REM sleep facilitates fear extinction memory

Rapid eye movement (REM) sleep is known to facilitate fear extinction and play a protective role against fearful memories. 1 Colvonen P.J. Straus L.D. Acheson D. Gehrman P. A Review of the Relationship Between Emotional Learning and Memory, Sleep, and PTSD. Curr. Psychiatry Rep. 2019; 21: 2https://doi.org/10.1007/s11920-019-0987-2 Crossref PubMed Scopus (56) Google Scholar ,2 Pace-Schott E.F. Germain A. Milad M.R. Effects of sleep on memory for conditioned fear and fear extinction. Psychol. Bull. 2015; 141: 835-857https://doi.org/10.1037/bul0000014 Crossref PubMed Scopus (158) Google Scholar Consequently, disruption of REM sleep after a traumatic event may increase the risk for developing PTSD. 3 Koren D. Arnon I. Lavie P. Klein E. Sleep Complaints as Early Predictors of Posttraumatic Stress Disorder: A 1-Year Prospective Study of Injured Survivors of Motor Vehicle Accidents. Am. J. Psychiatry. 2002; 159: 855-857https://doi.org/10.1176/appi.ajp.159.5.855 Crossref PubMed Scopus (309) Google Scholar ,4 Mellman T.A. Pigeon W.R. Nowell P.D. Nolan B. Relationships between REM sleep findings and PTSD symptoms during the early aftermath of trauma. J. Trauma Stress. 2007; 20: 893-901https://doi.org/10.1002/jts.20246 Crossref PubMed Scopus (170) Google Scholar However, the underlying mechanisms by which REM sleep promotes extinction of aversive memories remain largely unknown. The infralimbic cortex (IL) is a key brain structure for the consolidation of extinction memory. 5 Milad M.R. Quirk G.J. Fear extinction as a model for translational neuroscience: ten years of progress. Annu. Rev. Psychol. 2012; 63: 129-151https://doi.org/10.1146/annurev.psych.121208.131631 Crossref PubMed Scopus (1083) Google Scholar Using calcium imaging, we found in mice that most IL pyramidal neurons are intensively activated during REM sleep. Optogenetically suppressing the IL specifically during REM sleep within a 4-h window after auditory-cued fear conditioning impaired extinction memory consolidation. In contrast, REM-specific IL inhibition after extinction learning did not affect the extinction memory. Whole-cell patch-clamp recordings demonstrated that inactivating IL neurons during REM sleep depresses their excitability. Together, our findings suggest that REM sleep after fear conditioning facilitates fear extinction by enhancing IL excitability and highlight the importance of REM sleep in the aftermath of traumatic events for protecting against traumatic memories.