Biological clock may shut down long-term memory at night

If you crammed for tests by pulling ‘all nighters’ in school, ever wonder why your memory is now a bit foggy on what you learned? A University of Houston professor may have the answer with his research on the role of circadian rhythms in long-term learning and memory.

Arnold Eskin, the John and Rebecca Moores Professor of Biology and Biochemistry at UH, was recently awarded two grants totaling $2,472,528 from the National Institutes of Health (NIH) to continue pursuing his investigations of memory formation and the impact of the biological clock on learning and memory.

Scientists have known for a while that the brain’s biological (or circadian) clock influences natural body cycles, such as sleep and wakefulness, metabolic rate and body temperature. New research from Eskin suggests the circadian clock also may regulate the formation of memory at night. This new research focuses on “Circadian Modulation of Long-term Memory Formation” and “Long-term Regulation of Glutamate Uptake in Aplysia,” with NIH funding to be disbursed over four years.

“There is a lot of research going on in memory,” Eskin said. “How do we remember things given that we don’t have a camera in our brain to record events? What changes take place in our brains that allow us to remember? These grants are about fundamental learning and memory and about modulation of memory.”

For the grant on circadian modulation of long-term memory formation, Eskin will continue studies based on his data that reveal the circadian clock modulates several forms of long-term memory in the marine snail Aplysia.

These studies involved experiments on the defensive reflexes and feeding responses of Aplysia. Eskin’s results showed that Aplysia form long-term memory when they are trained during the day but not when they are trained at night. However, short-term memory of the same behaviors is formed equally well during the day and night, which might explain why all-night cram sessions may have helped you get through certain classes in school, but did not leave you with enough of a lasting impression to become part of your long-term store of knowledge.

“Somewhere in the molecular circuit, in the neural circuit in the brain, the biological clock is shutting that circuit off at a particular time of night. It’s shutting molecules down so that long-term memory can’t happen,” Eskin said.

Lisa Lyons, a research assistant professor at UH, is the primary investigator on this grant and is already investigating molecules involved in memory formation that might be activated during the day but not at night. NIH funding will help advance the pursuit of this line of research.

For the grant on long-term regulation of glutamate uptake in Aplysia, Eskin will focus on the transmitter substance glutamate, which is involved in memory formation.

“The formation of memory happens at places in the brain called synapses, where cells ‘talk’ to one another through the release of chemicals called transmitter substances,” Eskin said. “In order for transmitters to work, once they are released they have got to be cleared away so that others can subsequently act. So, there are not only important mechanisms to release the transmitters, but also mechanisms to get rid of them, and these are called reuptake systems.”

Eskin is studying glutamate reuptake and glutamate transport to understand the mechanism or change that takes place at the synapses of nerve cells (or neurons) that enables people to remember. In previous research, Eskin found that glutamate transport molecules, which act as the brain’s cleaning crew during learning and memory formation, actually increase once the long-term memory-forming process begins. Deficiencies in these glutamate transporters that affect the strength of connections among the neurons associated with memory may explain why memory lapses such as forgetting where you last set down your keys occur.

“This research will provide significant information toward understanding memory and thus diseases that affect memory,” Eskin said.

With the potential to shed light upon neurodegenerative diseases such as Alzheimer’s - marked by a loss of brain function due to the deterioration of neurons - studying these nerve cells could one day take this research from helping you be better able to find your glasses to providing relief from a debilitating illness.

“At the end of the day, we can’t make memory better or improve it unless we understand how memory works and is modulated,” he said. “That’s what this research is all about.”

He is currently completing the last year of another NIH-funded grant on “Glutamate Transport Regulation and Synaptic Plasticity” that complements these two new grants, but investigates the role of glutamate uptake in associative learning in mammals. This research project on mammals represents a great example of traslational research in which basic findings in a simple system (i.e. Aplysia) were quickly applied to a higher organism (i.e. mammals). They found that glutamate transport increased in the brains of mammals during learning as also found in Aplysia. (See related release at http://www.uh.edu/admin/media/nr/2002/032002/eskinlearning.html.)

Coming to UH more than 25 years ago, Eskin guided the merger of two departments into what is now the Department of Biology and Biochemistry in the College of Natural Sciences and Mathematics. As department chair from 1994 to 2000, Eskin tripled research grants to approximately $6 million per year and developed the department’s research foci of neuroscience, the biological clocks and infectious disease. The author or co-author of more than 150 publications, he has received numerous honors, including the Esther Farfel Award, the university’s highest faculty honor. He is the only faculty member to receive both the Farfel Award and the Moores Professorship in the same year. Eskin earned his bachelor’s degree in physics from Vanderbilt University and his doctorate in zoology from the University of Texas.

UH’s Biological Clocks Program is one of the world’s leading centers for circadian rhythms research, with five laboratories and a team of more than 30 scholars. In addition to Eskin, the group is led by four other tenured faculty members in the biology and biochemistry department - Associate Professor Gregory M. Cahill, Professor Stuart Dryer, Professor Paul Hardin and Professor Michael Rea. For more information on the biological clocks program at UH, visit http://www.bchs.uh.edu/research_clocks.htm

Ginkgo Extract May Improve Cognition and Decrease Stress for Computer Users

Reviewed: Kaschel R, Hoerr R, Kresimon J, Rychlik R. The influence of ginkgo special extract EGb 761� on the performance of healthy subjects at computer workstations�open-label clinical study in pre-post design with a control group. Translation from J Pharmako u Ther. 2007;Jan:3-9.
Clinical studies have shown that ginkgo (Ginkgo biloba, Ginkgoaceae) can improve cognitive performance and stress tolerance in healthy people and in elderly people with dementia. Studies using the special ginkgo extract EGb 761� have demonstrated improvements in brain function, emotional stability, mental capacity, attention, and coping with stress in healthy people. People who work at computer workstations for much of the day may suffer from health disorders such as fatigue, lack of concentration, irritability, and mental stress. The purpose of this study was to investigate the effects of EGb 761 on the performance of healthy people at computer workstations and to identify suitable tests to evaluate those effects.

The study was an open-label pilot study involving healthy people who were 45 years of age or older and who spent at least 50% of their workday in front of a computer. The study was conducted by researchers from the University of Osnabruck in Germany. Following a 2-week run-in period in which the subjects were trained on specific computer tests, the subjects completed baseline measurements of reaction capacity, sustained attention, eyesight sensitivity, stress perception, and quality of life. After the baseline measurements, subjects were allowed to choose if they wanted to be in the control group receiving no ginkgo or in the treatment group receiving 120 mg of ginkgo extract EGb 761 twice daily for 8 weeks (Tebonin�; Dr. Willmar Schwabe GmbH & Co., Karlsruhe, Germany). All subjects repeated the baseline tests after the 8-week treatment period ended, and the tolerability of EGb 761 was assessed.

The study enrolled 104 subjects, 84 of which completed the study according to the protocol. In the sustained attention test (a measure of long-term concentration) the number of errors made by subjects in the ginkgo group decreased significantly after 8 weeks compared to the control group (P = 0.035). Perceived stress scores improved significantly in the ginkgo group (P = 0.007), and the �vitality� portion of the quality of life evaluation improved significantly in the ginkgo group (P = 0.004) compared to the control group. No significant differences were found between the 2 groups for reaction capacity after the 8-week treatment period. No serious adverse events were reported for either group, and the tolerability of EGb 761 was judged to be good.

The authors conclude that EGb 761 treatment produced clear objective and subjective improvements in concentration, perceived stress, and quality of life in people working at computer workstations much of the day. The authors assess the results to be particularly significant for people over 45 years of age, because that population group is more likely to perceive computer work as more stressful than a younger population. The authors recommend that a more extensive double-blind trial should be conducted using the tests identified in this study.

The results of this study are consistent with previous studies showing improvements in cognitive performance and stress tolerance. However, the authors provide results for only one of the eight �domains� of the quality of life evaluation (the SF-36 Health Survey). It is not known if ginkgo supplementation had any effect on the remaining seven domains, and this would be of interest to other researchers and readers.

The authors state that the results show that improvements relevant to everyday functioning at work may be attained with EGb 761 treatment, in conjunction with an increase in stress reduction and quality of life.

Since the participants could choose which group they wanted to be in, there is a high likelihood that those entering the ginkgo group had a strong bias towards the efficacy of ginkgo. The control group is not only a control for ginkgo but also a control for a placebo effect. There is no way to know if the improvements were due to ginkgo or placebo effect. This study was financed by the ginkgo manufacturer and supported by an insurance association.