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KAIST researchers discovers the neural circuit that reacts to alarm clock
KAIST (President Kwang Hyung Lee) announced on the 20th that a research team led by Professor Daesoo Kim of the Department of Brain and Cognitive Sciences and Dr. Jeongjin Kim 's team from the Korea Institute of Science and Technology (KIST) have identified the principle of awakening animals by responding to sounds even while sleeping.
Sleep is a very important physiological process that organizes brain activity and maintains health. During sleep, the function of sensory nerves is blocked, so the ability to detect danger in the proximity is reduced. However, many animals detect approaching predators and respond even while sleeping. Scientists thought that animals ready for danger by alternating between deep sleep and light sleep.
A research team led by Professor Daesoo Kim at KAIST discovered that animals have neural circuits that respond to sounds even during deep sleep. While awake, the medial geniculate thalamus responds to sounds, but during deep sleep, or Non-REM sleep, the Mediodorsal thalamus responds to sounds to wake up the brain.
As a result of the study, when the rats fell into deep sleep, the nerves of the medial geniculate thalamus were also sleeping, but the nerves of mediodorsal thalamus were awake and responded immediately to sounds. In addition, it was observed that when mediodorsal thalamus was inhibited, the rats could not wake up even when a sound was heard, and when the mediodorsal thalamus was stimulated, the rats woke up within a few seconds without sound.
This is the first study to show that sleep and wakefulness can transmit auditory signals through different neural circuits, and was reported in the international journal, Current Biology on February 7, and was highlighted by Nature. (https://www.nature.com/articles/d41586-023-00354-0)
Professor Daesoo Kim explained, “The findings of this study can used in developing digital healthcare technologies to be used to improve understanding of disorders of senses and wakefulness seen in various brain diseases and to control the senses in the future.”
This research was carried out with the support from the National Research Foundation of Korea's Mid-Career Research Foundation Program.
Figure 1. Traditionally, sound signals were thought to be propagated from the auditory nerve to the auditory thalamus. However, while in slow-wave sleep, the auditory nerve sends sound signals to the mediodorsal thalamic neurons via the brainstem nerve to induce arousal in the brain.
Figure 2. GRIK4 dorsomedial nerve in response to sound stimulation. The awakening effect is induced as the activity of the GRIK4 dorsal medial nerve increases based on the time when sound stimulation is given.
2023.03.03 View 3739 -
Mystery Solved with Math: Cytoplasmic Traffic Jam Disrupts Sleep-Wake Cycles
KAIST mathematicians and their collaborators at Florida State University have identified the principle of how aging and diseases like dementia and obesity cause sleep disorders. A combination of mathematical modelling and experiments demonstrated that the cytoplasmic congestion caused by aging, dementia, and/or obesity disrupts the circadian rhythms in the human body and leads to irregular sleep-wake cycles. This finding suggests new treatment strategies for addressing unstable sleep-wake cycles.
Human bodies adjust sleep schedules in accordance with the ‘circadian rhythms’, which are regulated by our time keeping system, the ‘circadian clock’. This clock tells our body when to rest by generating the 24-hour rhythms of a protein called PERIOD (PER) (See Figure 1).
The amount of the PER protein increases for half of the day and then decreases for the remaining half. The principle is that the PER protein accumulating in the cytoplasm for several hours enters the cell nucleus all at once, hindering the transcription of PER genes and thereby reducing the amount of PER.
However, it has remained a mystery how thousands of PER molecules can simultaneously enter into the nucleus in a complex cell environment where a variety of materials co-exist and can interfere with the motion of PER. This would be like finding a way for thousands of employees from all over New York City to enter an office building at the same time every day.
A group of researchers led by Professor Jae Kyoung Kim from the KAIST Department of Mathematical Sciences solved the mystery by developing a spatiotemporal and probabilistic model that describes the motion of PER molecules in a cell environment.
This study was conducted in collaboration with Professor Choogon Lee’s group from Florida State University, where the experiments were carried out, and the results were published in the Proceedings of the National Academy of Sciences (PNAS) last month.
The joint research team’s spatial stochastic model (See Figure 2) described the motion of PER molecules in cells and demonstrated that the PER molecule should be sufficiently condensed around the cell nucleus to be phosphorylated simultaneously and enter the nucleus together (See Figure 3 Left). Thanks to this phosphorylation synchronization switch, thousands of PER molecules can enter the nucleus at the same time every day and maintain stable circadian rhythms.
However, when aging and/or diseases including dementia and obesity cause the cytoplasm to become congested with increased cytoplasmic obstacles such as protein aggregates and fat vacuoles, it hinders the timely condensation of PER molecules around the cell nucleus (See Figure 3 Right). As a result, the phosphorylation synchronization switch does not work and PER proteins enter into the nucleus at irregular times, making the circadian rhythms and sleep-wake cycles unstable, the study revealed.
Professor Kim said, “As a mathematician, I am excited to help enable the advancement of new treatment strategies that can improve the lives of so many patients who suffer from irregular sleep-wake cycles. Taking these findings as an opportunity, I hope to see more active interchanges of ideas and collaboration between mathematical and biological sciences.”
This work was supported by the National Institutes of Health and the National Science Foundation in the US, and the International Human Frontiers Science Program Organization and the National Research Foundation of Korea.
Publication:
Beesley, S. and Kim, D. W, et al. (2020) Wake-sleep cycles are severely disrupted by diseases affecting cytoplasmic homeostasis. Proceedings of the National Academy of Sciences (PNAS), Vol. 117, No. 45, 28402-28411. Available online at https://doi.org/10.1073/pnas.2003524117
Profile:
Jae Kyoung Kim, Ph.D.
Associate Professor
jaekkim@kaist.ac.kr
http://mathsci.kaist.ac.kr/~jaekkim
@umichkim on Twitter
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
Profile:
Choogon Lee, Ph.D.
Associate Professor
clee@neuro.fsu.edu
https://med.fsu.edu/biosci/lee-lab
Department of Biomedical Sciences
Florida State University
Florida, USA
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2020.12.11 View 8320 -
New Scientist: Wind power harnesses the energy of galloping, June 2, 2011
Researchers from the Civil and Environmental Engineering Department, KAIST, released their research results in Smart Materials and Structures on ways to “harness strange properties of turbulent airs.” They built a prototype that produces energy using a specific type of unstable airflow called “wake galloping.” New Scientist wrote an article about the paper, which appeared on June 2, 2011. For the article, please follow the link below.
http://www.newscientist.com/article/mg21028145.700-wind-power-harnesses-the-energy-of-galloping.html?full=true&print=true
2011.06.04 View 8067 -
Waking Up Is Hard to Do: Scientists have discovered a new mechanism in the core gears of the circadian clock.
The US News & World Report released an article (Feb. 18, 2011) on KAIST’s research collaboration with Northwestern University in the US to identify a gene that regulates the rhythm of a fruit fly’s circadian clock, which may be applied to explain human’s sleep-wake cycle. The research result was published February 17 in the journal Nature.
For the link of the US News & World Report article, please go to the following link:
http://www.usnews.com/science/articles/2011/02/18/waking-up-is-hard-to-do_print.html
2011.02.21 View 9490