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Randy J. Nelson is an American neuroscientist who holds the Hazel Ruby McQuain Chair for Neurological Research and the founding chair of the Department of Neuroscience at the West Virginia University School of Medicine. [1] Much of his research has focused on the contribution of circadian and seasonal rhythms on physiology and behavior.
Nelson graduated from James A. Garfield High School in Garrettsville, Ohio in 1972. He earned his bachelor's degree in psychology at the University of California, Berkeley in 1978, and then a master's degree from Berkeley in 1980. Trained under Irving Zucker, Nelson then earned a PhD in Psychology, as well as a second PhD in Endocrinology, also from Berkeley. He then completed an NIH-funded postdoctoral fellowship at the University of Texas, Austin.
Although his dissertation advisor's lab was known for studies in circadian rhythms, Nelson started working on photoperiodism (day length) and seasonality. He investigated the mechanisms that allow rodents to measure day length to determine the time of year in order to anticipate predictable events, such as winter, to initiate temporally-important adaptations such as reproductive, metabolic, and immune adjustments. During his postdoctoral studies, he established the roles of additional environmental signals that fine-tuned the timing of seasonality.
Nelson was appointed to the faculty in psychology and neuroscience at Johns Hopkins University from 1986 until 2000, when he moved to the Ohio State University (OSU) where he was Professor and Chair of the Department of Neuroscience. In 2012, he was appointed as the inaugural Distinguished Professor of the College of Medicine, and in 2013 the Board of Trustees conferred the title of Distinguished University Professor upon him.
Nelson has conducted research in four fields (1) seasonality in physiology and behavior, (2) photoperiodism and immune function (3), circadian rhythms and sleep, and (4) aggression). Although much of his early research was on reproductive physiology and behavior, his lab started to use day length as a precise environmental probe to elicit season-specific changes in brain and behavior. His group demonstrated that short days impair spatial learning and memory by dampening LTP. Indeed the hippocampus is reduced in size in short days or by melatonin treatment that mimics short days. He also demonstrated that blood flow into the hippocampus is curtailed by short days, which may drive the reduction in neurogenesis that has been reported.
At Johns Hopkins, Nelson formed important collaborations with Solomon Snyder among others in the burgeoning field of understanding the behavioral role of specific gene products. He had a role in identifying genes involved in the regulation of motivated behaviors such as aggression and reproduction. For example, in the early stages of the “transgenic mouse revolution”, he and his Hopkins colleague published a comprehensive series of studies detailing the effects on nitric oxide (NO), at the time a novel neural modulator, on behavior. [2] They established a large increase in aggressive behavior and excessive, inappropriate sexual behavior in transgenic mice lacking the NOS gene, which suggested that NO normally forms a behavioral 'brake' on impulsive, motivated behaviors. The functional significance of gaseous neuromodulators was established by this research. This original study was the first comprehensive behavioral phenotyping study in a transgenic mouse. It has been cited over 900 times and provoked much basic research into the biological bases underlying aggression.
Nelson contributed to the development of the subdiscipline of ecoimmunology. [3] With many collaborators, he identified the mechanisms by which immune systems are bolstered to counteract seasonally-recurrent stressors, such as low temperature or food shortages. In this context, he has studied stress, infectious diseases, autoimmune diseases, and cancers, as well as the role of hormones, such as melatonin and glucocorticoids. His group has documented that animals, including humans, monitor day length (photoperiod) to engage seasonally appropriate adaptations in anticipation of harsh winter conditions. They proposed that photoperiodic information, mediated by melatonin, also influenced immune responses. Individuals could improve survival if seasonally recurring stressors were anticipated and countered. This 20 year-long series of studies suggest that short day lengths (i.e. winter conditions) reroute energy from reproduction and growth to bolster immune function. [4] The net result of these photoperiod-mediated adjustments is enhanced immune function and increased survival. This work has important implications for understanding the dynamics of the influenza season, as well as other emergent seasonal diseases.
More recently, Nelson focused on the effects of dim light at night on the disruption of circadian rhythms to examine a number of outcomes, including obesity, depression, cognition, cardiac disease, and cancer. His lab has established that exposure to dim light at night disrupts the expression of circadian clock gene expression, provokes neuroinflammation, and increases body mass gain and depressive-like responses, as well as impairs cognition, immune function, and recovery from cardiac arrest and stroke.
He has been elected as a fellow the American Association for the Advancement of Science, the American Psychological Association, the Association for Psychological Science, and the Animal Behavior Society.
he received the Education Award from the Society for Neuroscience in 2017. Among his notable trainees are Sabra Klein and Staci Bilbo,
An Introduction to Behavioral Endocrinology, [5] a leading textbook ,
Nelson, R.J. 2019. (Hormones and Behavior section editor). Encyclopedia of Animal Behavior. Second Edition. Elsevier Major Reference Works, Oxford, UK.
Nelson, R.J. (Editor). 2022. Encyclopedia of Neuroscience. Oxford University Press.
Nelson, R.J. & Kriegsfeld, L.J. 2022. An Introduction to Behavioral Endocrinology. Sixth Edition. Sinauer Associates, An imprint of Oxford University Press: Sunderland, MA.
Fonken, L.F. & Nelson, R.J. (Editors). 2023. Biological Implications of Circadian Disruption: A Modern Health Challenge. Cambridge University Press (In press).
Nelson, R.J. & Weil, Z.M. (Editors). 2023. Biographical History of Behavioral Neuroendocrinology. Springer Nature, New York.
Bedrosian, T.A. & Nelson, R.J. 2017. Timing of light exposure affects mood and brain circuits. Translational Psychiatry, 7: e1017. PM28140399. •
Borniger, J.C., Walker, W.H., Gaudier-Diaz, M.M., Stegman, C., Zhang, N., Hollyfield, J.L., Nelson, R.J. & DeVries, A.C. 2017. Time-of-day dictates transcriptional inflammatory responses to cytotoxic chemotherapy. Scientific Reports , 7:1-11. PM28117419. •
Cisse, YM, Russart, KL, & Nelson, RJ. 2017. Parental exposure to dim light at night prior to mating alters offspring adaptive immunity. Scientific Reports, 31:1-10. PM28361901. •
Borniger J.C., Walker W.H., Surbhi, Emmer K.M., Zhang N., Zalenski A.A., Muscarella S.L., Fitzgerald J.A., Smith A.N., Braam C., Tial T., Magalang U., Lustberg M.B., Nelson RJ., DeVries A.C. 2018. A role for hypocretin/orexin in metabolic dysfunction in a mouse model of non-metastatic breast cancer. Cell Metabolism , 27:1-12. A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer. •
Fonken, L.K., Bedrosian, T.A., Zhang, N., Weil, Z.M., DeVries, A.C., & Nelson, R.J. 2019. Dim light at night impairs recovery from global cerebral ischemia. Experimental Neurology , 317:100-109. doi.org/10.1016/j.expneurol.2019.02.008 •
Walker, W.H., Zhang, N., Melendez-Hernandez, O.H., Pascoe, J., DeVries, A.C., & Nelson, R.J. 2020. Acute exposure to dim light at night is sufficient to induce neurological changes and depressive-like behavior. Molecular Psychiatry , 25: 1080–1093. doi: 10.1038/ s41380-019-0430-4 •
Walker, W.H., Walton, J.C., DeVries, A.C., & Nelson, R.J. 2020. Circadian rhythm disruption and mental health. Translational Psychiatry, 10:28 doi: 10.1038/s41398-020-0694-0.
Nelson is married to A. Courtney DeVries, a prominent stress biologist. They have two sons.
A circadian rhythm, or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism and responds to the environment. Circadian rhythms are regulated by a circadian clock whose primary function is to rhythmically co-ordinate biological processes so they occur at the correct time to maximize the fitness of an individual. Circadian rhythms have been widely observed in animals, plants, fungi and cyanobacteria and there is evidence that they evolved independently in each of these kingdoms of life.
Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobiology comes from the ancient Greek χρόνος, and biology, which pertains to the study, or science, of life. The related terms chronomics and chronome have been used in some cases to describe either the molecular mechanisms involved in chronobiological phenomena or the more quantitative aspects of chronobiology, particularly where comparison of cycles between organisms is required.
Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cows that could induce skin lightening in common frogs. This compound was later identified as a hormone secreted in the brain during the night, playing a crucial role in regulating the sleep-wake cycle, also known as the circadian rhythm, in vertebrates.
A major organ of the endocrine system, the anterior pituitary is the glandular, anterior lobe that together with the posterior lobe makes up the pituitary gland (hypophysis) which, in humans, is located at the base of the brain, protruding off the bottom of the hypothalamus.
Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.
A phase response curve (PRC) illustrates the transient change in the cycle period of an oscillation induced by a perturbation as a function of the phase at which it is received. PRCs are used in various fields; examples of biological oscillations are the heartbeat, circadian rhythms, and the regular, repetitive firing observed in some neurons in the absence of noise.
Photoperiod is the change of day length around the seasons. The rotation of the earth around its axis produces 24 hour changes in light (day) and dark (night) cycles on earth. The length of the light and dark in each phase varies across the seasons due to the tilt of the earth around its axis. The photoperiod defines the length of the light, for example a summer day the length of light could be 16 hours while the dark is 8 hours, whereas a winter day the length of day could be 8 hours, whereas the dark is 16 hours. Importantly, the seasons are different in the northern hemisphere than the southern hemisphere.
Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence of an additional photoreceptor was first suspected in 1927 when mice lacking rods and cones still responded to changing light levels through pupil constriction; this suggested that rods and cones are not the only light-sensitive tissue. However, it was unclear whether this light sensitivity arose from an additional retinal photoreceptor or elsewhere in the body. Recent research has shown that these retinal ganglion cells, unlike other retinal ganglion cells, are intrinsically photosensitive due to the presence of melanopsin, a light-sensitive protein. Therefore, they constitute a third class of photoreceptors, in addition to rod and cone cells.
Melatonin receptor type 1A is a protein that in humans is encoded by the MTNR1A gene.
Light effects on circadian rhythm are the response of circadian rhythms to light.
Sundowning, or sundown syndrome, is a neurological phenomenon associated with increased confusion and restlessness in people with delirium or some form of dementia. It is most commonly associated with Alzheimer's disease but is also found in those with other forms of dementia. The term sundowning was coined by nurse Lois K. Evans in 1987 due to the timing of the person's increased confusion beginning in the late afternoon and early evening. For people with sundown syndrome, a multitude of behavioral problems begin to occur and are associated with long-term adverse outcomes. Sundowning seems to occur more frequently during the middle stages of Alzheimer's disease and mixed dementia and seems to subside with the progression of the person's dementia. People are generally able to understand that this behavioral pattern is abnormal. Research shows that 20–45% of people with Alzheimer's will experience some variation of sundowning confusion. However, despite lack of an official diagnosis of sundown syndrome in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), there is currently a wide range of reported prevalence.
Designing lighting for the elderly requires special consideration and care from architects and lighting designers. As people age, they experience neurodegeneration in the retina and in the suprachiasmatic nucleus (SCN). Less light reaches the back of the eyes because the pupils decrease in size as one ages, the lens inside one's eye becomes thicker, and the lens scatters more light, causing objects and colors to appear less vivid. These symptoms are particularly common with persons having alzheimer's disease. Older people also have reduced levels of retinal illuminance, such as having smaller pupils and less transparent crystalline lenses. Furthermore, as an individual ages, they begins to lose retinal neurons, which not only compromises the ability to see but also to register a robust daily pattern of light-dark that is needed to maintain biological rhythms. The 24-hour light-dark cycle is the most important external stimulus for regulating the timing of the circadian cycle.
Michael Terman is an American psychologist best known for his work in applying the biological principles of the circadian timing system to psychiatric treatments for depression and sleep disorders. This subspecialty is known as Chronotherapeutics.
Douglas G. McMahon is a professor of Biological Sciences and Pharmacology at Vanderbilt University. McMahon has contributed several important discoveries to the field of chronobiology and vision. His research focuses on connecting the anatomical location in the brain to specific behaviors. As a graduate student under Gene Block, McMahon identified that the basal retinal neurons (BRNs) of the molluscan eye exhibited circadian rhythms in spike frequency and membrane potential, indicating they are the clock neurons. He became the 1986 winner of the Society for Neuroscience's Donald B. Lindsley Prize in Behavioral Neuroscience for his work. Later, he moved on to investigate visual, circadian, and serotonergic mechanisms of neuroplasticity. In addition, he helped find that constant light can desynchronize the circadian cells in the suprachiasmatic nucleus (SCN). He has always been interested in the underlying causes of behavior and examining the long term changes in behavior and physiology in the neurological modular system. McMahon helped identifying a retrograde neurotransmission system in the retina involving the melanopsin containing ganglion cells and the retinal dopaminergic amacrine neurons.
In chronobiology, the circannual cycle is characterized by biological processes and behaviors recurring on an approximate annual basis, spanning a period of about one year. This term is particularly relevant in the analysis of seasonal environmental changes and their influence on the physiology, behavior, and life cycles of organisms. Adaptations observed in response to these circannual rhythms include fur color transformation, molting, migration, breeding, fattening and hibernation, all of which are inherently driven and synchronized with external environmental changes.
In the field of chronobiology, the dual circadian oscillator model refers to a model of entrainment initially proposed by Colin Pittendrigh and Serge Daan. The dual oscillator model suggests the presence of two coupled circadian oscillators: E (evening) and M (morning). The E oscillator is responsible for entraining the organism’s evening activity to dusk cues when the daylight fades, while the M oscillator is responsible for entraining the organism’s morning activity to dawn cues, when daylight increases. The E and M oscillators operate in an antiphase relationship. As the timing of the sun's position fluctuates over the course of the year, the oscillators' periods adjust accordingly. Other oscillators, including seasonal oscillators, have been found to work in conjunction with circadian oscillators in order to time different behaviors in organisms such as fruit flies.
Staci Bilbo is an American neuroimmunologist and The Haley Family Professor of Psychology and Neuroscience at Duke University. Bilbo also holds a position as a research affiliate at Massachusetts General Hospital overseeing research within the Lurie Center for Autism. As the principal investigator of the Bilbo Lab, Bilbo investigates how environmental challenges during the perinatal period impact the immune system and further influence brain development, cognition, and affective behaviors later in life..
Sato Honma is a Japanese chronobiologist who researches the biological mechanisms of circadian rhythms. She mainly collaborates with Ken-Ichi Honma on publications, and both of their primary research focuses are the human circadian clock under temporal isolation and the mammalian suprachiasmatic nucleus (SCN), its components, and associates. Honma is a retired professor at the Hokkaido University School of Medicine in Sapporo, Japan. She received her Ph.D. in physiology from Hokkaido University. She taught physiology at the School of Medicine and then at the Research and Education Center for Brain Science at Hokkaido University. She is currently the director at the Center for Sleep and Circadian Rhythm Disorders at Sapporo Hanazono Hospital and works as a somnologist.
Dr. Debra J. Skene is a chronobiologist with specific interest in the mammalian circadian rhythm and the consequences of disturbing the circadian system. She is also interested in finding their potential treatments for people who suffer from circadian misalignment. Skene and her team of researchers tackle these questions using animal models, clinical trials, and most recently, liquid chromatography-mass spectrometry. Most notably, Skene is credited for her evidence of a novel photopigment in humans, later discovered to be melanopsin. She was also involved in discovering links between human PER3 genotype and an extremely shifted sleep schedules categorized as extreme diurnal preference. Skene received her Bachelor of Pharmacy, Master of Science, and Ph.D. in South Africa.
Eberhard Gwinner was a German ornithologist and founding director of the Max-Planck Institute for ornithology. He specialized in the study of annual rhythms, their endocrine control, and biological clocks in birds.
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