Rats, REM and PTSD
Undergraduate Benjamin Laitman looks at the microarchitecture of sleep with fear conditioning.
B. Davin Stengel |
While everyone may be personally familiar with the phenomenon of sleep, few of us understand what transpires in our own brains between lights out and the sound of the morning alarm. More than the absence of wakefulness or a period of rest, sleep is a complex brain state of great interest to scientists and medical practitioners working in a variety of fields. Among these interested parties is Benjamin Laitman, C’10, a Biological Basis of Behavior and Anthropology major whose area of research may one day contribute to the development of new or improved clinical treatments for those suffering with post-traumatic stress disorder (PTSD).
In the laboratory of Emeritus Professor of Animal Biology Adrian Morrison and Professor of Psychiatry Richard Ross, Laitman has been working on developing an animal model of sleep disturbance in PTSD. “Insomnia and repetitive nightmares are highly prevalent in individuals with PTSD,” he explains, “and these symptoms are often intractable to available treatments.”
To better understand what is happening in the sleep-disturbed brains of humans with PTSD, Laitman—together with Jamie DaSilva, a graduate student at the University of the Sciences in Philadelphia, and her advisor, Professor of Pharmacology and Toxicology Shanaz Tejani-Butt—conducted an experiment with two rat strains: the Wistar-Kyoto rat (WKY), which is known to be particularly sensitive to stress, and the “normal” Wistar rat (WIS), which is thought to be less so.
“We recorded baseline sleep for four hours,” says Laitman, “and then the following day we conditioned the rats by pairing tones with a mild electrical shock. One day later, and again after two weeks, we recorded the rats’ sleep for four hours after a presentation of the fearful tones.”
What they found was that the rapid eye movement (REM) sleep—commonly known as “dream sleep”—of fear-conditioned WKY rats showed greater fragmentation compared to that of fear-conditioned WIS rats. The number of muscle twitches during REM sleep also showed a greater increase in the WKY rats after fear conditioning. According to Laitman, these findings suggest a relation to the sleep of humans with PTSD, who show more REM sleep interruptions and more phasic muscle activity during REM sleep than non-PTSD individuals.
“One possible explanation for REM fragmentation in the aftermath of fear conditioning is an increase in central nervous system noradrenergic activity,” says Laitman, “which is normally low to nonexistent during REM sleep.”
In order to test this hypothesis, Laitman measured heart rate during REM sleep as a potential indicator of sympathetic noradrenergic activity. What he found was that fear conditioning increased heart rate during REM sleep in both rat strains, but much more so in the stress-sensitive WKY rats than in the WIS rats. Because such an increase could be caused either by increased sympathetic nervous system activity or by decreased parasympathetic nervous system activity, Laitman is now working with Bioengineering major Matthew DiFrancesco, EAS’10, who is devising a program to analyze heart rate variability in Laitman’s data to distinguish between these two possibilities.
Laitman will present his work on REM heart rate changes at the Associated Professional Sleep Societies’ annual meeting in June. In the meantime, he is also conducting research on REM sleep termination, looking at electroencephalograms and using power spectral analysis to identify which frequency ranges are prevalent during different sleep stages—both before and after fear conditioning and between the WKY and WIS rat strains.
Clinical applications for human patients may not be imminent, but Laitman feels good about working in an area that might one day help individuals with PTSD lead more productive and fulfilling lives. “As we’re seeing with soldiers coming home from Iraq and Afghanistan,” Laitman says, “PTSD is a real problem.” According to a 2008 study by the Rand Corporation, 14% of returning service members who were deployed for Operations Enduring Freedom and Iraqi Freedom currently meet the criteria for PTSD.