Unlocking the Secrets of Sleep

By Sophia Marcom

Image by Jose Luis Navarro [CC-BY-NC-SA 4.0]

The average person spends about one third of their life the brain could lead to significant medical advances. Followasleep, yet our knowledge of what actually happens ing this interest, he worked as a postdoctoral researcher in a during this time is still limited. Sleep is incredibly im- neuroscience lab at Johns Hopkins University from 2011 to portant for physical and mental health, but scientists do not 2017 before coming to UNC and starting his own lab. fully understand what actually happens in the brain that al- Dr. Diering’s research is geared toward understandlows one to wake up feeling refreshed and focused. As such, ing sleep disruption as it relates to diseases. While sleep disscientists all around the world are attempting to unlock the ruption is a part of many diseases, his research focuses on mystery of sleep. Some of the answers can be found right Alzheimer’s and Autism Spectrum Disorder specifically. Dr. here at UNC-Chapel Hill in Dr. Graham Diering’s neurosci- Diering’s goal is to better the lives of individuals with these ence lab. Dr. Diering and his team study sleep as it relates to diseases by improving their ability to sleep. He believes that neurodegenerative and neurodevelopmental diseases such poor sleep quality is a causative factor in the progression of as Alzheimer’s disease and Autism Spectrum Disorder re- these diseases. As he stated in an interview, “The idea is to spectively. The goal of their research is to develop a therapy develop some kind of a therapy to target sleep. But I want to give individuals with sleep issues the benefits of a good to be clear that the kind of therapy I’m talking about is not night’s rest. However, in order to mimic the effects of a good some sedative that would just make you want to lie down. night’s sleep, they must I’m talking about some kind of therapy that would really give first identify what hap- you the benefits of a good night’s sleep. A kind of a drug pens during sleep. that’s based on detailed knowledge of what sleep is doing.” Dr. Graham Dier1 The kind of medicine that Dr. Diering describes does not ing, an assistant profes- currently exist, so many people resort to sleeping pills that sor in UNC’s department act as sedatives but are unable to mimic the benefits of natuof Cell Biology and Physi- ral sleep. With a deeper understanding of the basis of sleep’s ology, started out his ca- restorative patterns, scientists could design revolutionarily reer at the University of effective medicines that would be useful in many types of British Columbia in the diseases. early 2000s. Though orig- While working in the neuroscience lab at Johns Hopinally interested in phys- kins, Dr. Diering came across a phenomenon that has helped ics, he gravitated towards him better understand brain activity during sleep: homeo-

Dr. Graham Diering, PhD biology throughout his static scaling, which is when neurons adapt their levels of undergraduate years and completed a PhD in biochemistry activity in response to certain stimuli by either increasing in 2011. During his PhD, he developed a strong interest in or decreasing their synaptic connections. The synapse is a neuroscience and learned that studying the intricacies of small gap separating neurons through which neurotrans32

Carolina Scientific pyschology & neuroscience mitters pass on nerve impulses. The regulation of synaptic symptoms.”1 With Alzheimer’s specifically, Dr. Diering hyactivity allows the brain to maintain stability and carry out pothesized that sleep quality is the first to take a hit during the appropriate level of function despite changing external onset. Knowing this information opens up the potential to conditions. Homeostatic scaling was described over 20 years deter or minimize more severe symptoms by starting theraago after being observed in in-vitro neurons, but labs all over pies to target and prioritize quality sleep. The cause-effect the world are currently working to discover how and when relationship between sleep quality and cognitive and social it happens in-vivo. While scaling up activity in the brain in behavior in autism is not well known, however, Dr. Diering response to an injury or disruption is commonly observed hopes to discover whether an improvement in sleep qualin-vivo, scaling down is not as well understood. Dr. Diering ity can lead to the recovery of some positive behaviors. His came across the hypothesis that the scaling down of synaptic lab uses a combination of in-vitro neuron models and inconnections occurs during sleep, and through experimenta- vivo mouse models to conduct this research. As they move tion, he found that to be the case. The hypothesis is known towards a disease focus, more specific mouse models are as “The Synaptic Homeostasis HYpothesis (SHY) of Sleep.”2 It being used that either have Alzheimer’s-like degeneration states that while humans are awake, synaptic connections or mimic the sleep disruption observed in autism. Mouse are strengthened; when one is asleep, the strengthening is models provide in-vivo models of homeostatic scaling and off-set by the weakening of synapses. Using SHY as a start- demonstrate that scaling-down is an essential component of ing point, Dr. Diering’s work moved towards a focus on dis- quality sleep. ease and sleep. He uses the idea of synaptic scaling as a basis for his understanding of the mechanisms and functions of sleep. According to Dr. Diering, one of the many purposes of sleep is to clear out all of the unimportant information humans take in during the day. He describes it as an “Etch A Sketch model,” saying “if you want to store new information on the next day, you have to shake all that stuff out and clean it away, and literally make new space to learn more things.” He describes forgetting as an intentional and necessary process, rather than a passive and disadvantageous one. “We talk about the brain’s ability to remember and the brain’s ability to form memory, and it’s pretty great. But actually,

Figure 1. A diagram showing the weakening of synaptic connections during sleep, as explained by the SHY hypothesis

we’re much better at forgetting. And I would say that 95% of the information that we take in does not get turned into long term memory and it’s forgotten.”1 The understanding of sleep as a way to clear necessary brain space sheds a light on the dangerous consequences of sleep deprivation and helped Dr. Diering’s lab make the connection between sleep disruption and the onset or worsening of many diseases. The research conducted by Dr. Diering goes in two major directions: one studying sleep at the end of life with Alzheimer’s disease and the other studying younger stages of life with autism. The diversity in his research shows that sleep is extremely important at all ages and can have drastic effects on quality of life. Dr. Diering started these research projects with the hypothesis that “sleep disruption is a core part of the disease that really does contribute to the other

Figure 2. Increasingly, researchers are recognizing sleep as one of the three “pillars” of health alongside nutrition and exercise. Image by Sarah Monroe

Due to the abundance of research being conducted on sleep, there is controversy present in the field. Dr. Diering explained that disagreements between scientists arise from the complicated nature of sleep – many processes occur during sleep that serve multiple purposes. There are also discrepancies between research done on differing age groups. Although sleep is important at all ages, many hypotheses that address sleep in one age group contradict patterns observed in other age groups. Looking at sleep from a developmental angle will help scientists reconcile their disagreements. As Diering said, “it’s a complicated business, sleep, just like being awake is a complicated business.”1 There is no easy way to explain all of the functions of sleep, but understanding the process of scaling down can assist scientists in developing effective treatments to improve the lives of those suffering from a wide variety of diseases.

References

1. Interview with Graham Diering, Ph.D. 4 September 2020. 2. Graham Diering. Diering Lab. http://dieringlab.web.unc. edu/research/ [accessed September 4, 2020]