REM Sleep Protects Against Fearful Memories
Post by Meagan Marks
The takeaway
REM sleep may protect against the development of post-traumatic stress disorder by enhancing the brain’s ability to extinguish fearful memories. It does so by strengthening the excitability of infralimbic cortex neurons, which play a crucial role in fear extinction.
What's the science?
Post-traumatic stress disorder (PTSD) often presents as persistent, uncontrollable fear responses triggered by cues associated with a past traumatic event. PTSD is likely caused by a neural disruption in fear extinction, which is the process of learning that a fear-inducing cue is no longer predictive of danger. Fear extinction is carried out by neurons in the infralimbic cortex (IL) in mice, which is homologous to the ventromedial prefrontal cortex in humans. It is a region highly active during rapid eye movement (REM) sleep. Interestingly, PTSD patients often experience disturbances in REM sleep, but the exact role that it plays in fear extinction remains unknown. This week in Current Biology, Hong and colleagues determine how REM sleep influences fear extinction, particularly through its influence over IL neuron excitability.
How did they do it?
To understand the paired role that REM sleep and IL neurons play in fear extinction, the authors conducted an experiment over the course of three days. On the first day, the mice were fear conditioned, learning that an auditory cue (20-second tone) would elicit an unpleasant stimulus (one-second foot shock). Immediately after this conditioning, the authors used optogenetics to silence the activity of IL neurons during sleep. At this stage, the mice were split into three groups: for one group, IL neurons were silenced only during REM sleep, while for another, the neurons were silenced immediately after REM sleep. A control group with no neural manipulation was also included.
On the second day, the mice were placed back in the fear conditioning environment, but this time, the auditory cue was played without a subsequent foot shock. This was a day of extinction learning, where the mice learned that the auditory cue should no longer induce fear.
On the third and final day, the auditory cue again played with no subsequent foot shock. This was a day of recall, where the authors observed how well the mice extinguished the fear association from the day before. They did so by measuring how long the mice froze after each auditory cue, an innate fear response in rodents.
Additionally, the authors repeated this paradigm twice more, with slight changes. During one repeat, the authors waited an additional four hours after conditioning to silence IL neurons during REM sleep. During the second, IL neurons were not silenced after fear conditioning but instead were immediately silenced after extinction learning.
What did they find?
The authors found that inhibiting IL activity during REM sleep post-conditioning significantly increased freezing time during recall. The control mice and mice with inhibition after REM sleep did not freeze as much, suggesting that IL activity during REM sleep is crucial to the consolidation of fear extinction memories. Delaying the post-conditioning inhibition of IL activity during REM sleep did not significantly alter freezing, nor did it inhibit IL neurons immediately after extinction learning.
Looking at these findings altogether, it can be concluded that IL neuron activity during REM sleep that occurs immediately after fear conditioning is crucial to fear extinction. This is because inhibiting IL neuron activity decreases the overall excitability of the neurons, and therefore, inhibiting IL neuron activity during all of REM sleep when the neurons are most active decreases their excitability the following day. This hindered their ability to fire during extinction learning, and the mice were less capable of encoding new fear extinction memories.
What's the impact?
This study found that REM sleep plays a crucial role in fear extinction by strengthening the excitability of IL neurons and enhancing their ability to encode new extinction memories. This is an important finding when it comes to PTSD, as many patients struggle with disturbances in REM sleep and experience reduced activity in extinction-encoding neurons. Knowing that REM sleep plays a pivotal role in extinction memory offers great potential in finding new therapies for PTSD and gives greater insight into the circuitry of fear extinction.