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Tag: Hokkaido University

  • Copper-doped tungstic acid nanocrystals transform infrared light conversion

    Copper-doped tungstic acid nanocrystals transform infrared light conversion

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    Newswise — Systematic copper doping boosts all-solar utilization in tungstic acid nanocrystals.

    Sunlight is an inexhaustible source of energy, and utilizing sunlight to generate electricity is one of the cornerstones of renewable energy. More than 40% of the sunlight that falls on earth is in the infrared, visible and ultraviolet spectra; however, current solar technology utilizes primarily visible and ultraviolet rays. Technology to utilize the full spectrum of solar radiation—called all-solar utilization—is still in its infancy.

    A team of researchers from Hokkaido University, led by Assistant Professor Melbert Jeem and Professor Seiichi Watanabe at the Faculty of Engineering, have synthesized tungstic acid-based materials doped with copper that exhibited all-solar utilization. Their findings were published in the journal Advanced Materials.

    “Currently, the near- and mid-infrared spectra of solar radiation, ranging from 800 nm to 2500 nm, is not utilized for energy generation,” explains Jeem. “Tungstic acid is a candidate for developing nanomaterials that can potentially utilize this spectrum, as it possesses a crystal structure with defects that absorb these wavelengths.”

    The team used a photo-fabrication technique they had previously developed, submerged photo-synthesis of crystallites, to synthesize tungstic acid nanocrystals doped with varying concentrations of copper. The structures and light-absorbing properties of these nanocrystals were analyzed; their photothermal, photo-assisted water evaporation, and photo-electrochemical characteristics were measured.

    The copper-doped tungsten oxide nanocrystals absorb light across the spectrum, from ultraviolet through visible light to infrared; the amount of infrared light absorbed was greatest at 1% copper doping. 1% and 5% copper-doped nanocrystals exhibited the highest temperature elevation (photothermal characteristic); 1% copper doped crystals also exhibited the greatest water evaporation efficacy, at approximately 1.0 kg per m2 per hour. Structural analysis of the 1% copper-doped nanocrystals indicated that the copper ions may be distorting the crystal structure of tungsten oxide, leading to the observed characteristics when light is absorbed.

    “Our discoveries mark a significant advance in advancement in the design of nanocrystallites capable of both synthesizing and harnessing all-solar energy,” concludes Watanabe. “We have demonstrated that copper doping grants tungstic acid nanocrystal a variety of characteristics via all-solar utilization. This provides a framework for further research in the field as well as for the development of applications.”

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  • Marine plankton and ecosystems affected by climate change

    Marine plankton and ecosystems affected by climate change

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    BYLINE: Naoki Namba

    Marine plankton plays an important role in the food chain, which is said to be undergoing a transformation due to climate change. Assistant Professor Kohei Matsuno of the Faculty of Fisheries Sciences spoke about how climate change is changing the distribution and ecology of marine plankton and what impact this will have on higher-trophic predators, including humans.

    The major role of microscopic plankton

    My research focuses on the effects of climate change on marine plankton in polar regions such as the Arctic and the Antarctic. Plankton are small, drifting creatures with weak swimming ability, that are basically just swept along by the water. They cannot move against ocean currents like fish, so they are directly affected by changes in ocean currents and the environment caused by climate change. In other words, the effects of climate change on plankton are easily observable.

    Another important aspect is the ability of phytoplankton to synthesize organic matter from inorganic matter through photosynthesis. Phytoplankton is then preyed upon by zooplankton, which is in turn preyed upon by fish, which are in turn eaten by higher predators such as birds. The small plankton support the marine ecosystem as primary producers. Beyond that, we humans also feed on marine products, so it can be said that plankton and we are connected.

    Climate change as reflected by plankton

    Arctic ice is now rapidly decreasing due to global warming. The reduction of sea ice and the inflow of melting water from glaciers should cause major changes in the marine environment, and we are investigating the effects of such changes on plankton. We actually go to the Arctic Ocean to collect plankton and continually study the number and types of plankton. Currently, satellite observations and mathematical modeling are being actively used for research, but field observations are an essential part of understanding the plankton in the ocean, and fieldwork is what I am best at.

    My research focuses on the Chukchi Sea, which is a part of the Arctic Ocean close to the Pacific Ocean. In this region, we know that warm water from the Pacific Ocean flows into the Arctic Ocean through the Bering Strait. This flow has strengthened in recent years, and we have found that there is a large influx of zooplankton from the Pacific Ocean into the Chukchi Sea. It has been shown that the increase in zooplankton due to the influx may increase the productivity of predators such as fish, and may also displace endemic plankton species that were originally present in the Arctic Ocean. Our research also showed that copepods, a type of zooplankton, brought from the Pacific Ocean, spawn and hatch in the Arctic Ocean. If the sea ice continues to decrease in the future and the influx of Pacific species increases and becomes established, this could drastically change the local ecosystem, including the impact on seals and polar bears.

    Untapped plankton research

    In fact, there are few studies on the relationship between climate change and plankton. Plankton research is difficult because you need to go to the field, and if you want to investigate the relationship with climate change, you need to accumulate data over a period of 20 or 30 years, which is time-consuming and very unglamorous research. That is why I find it interesting to work on it, because there are many things that no one has discovered yet.

    The situation has only recently become more data-intensive, but it is not easy to see the link with climate change because of the limited data available from the past. Conversely, if we don’t study the plankton in the Arctic and the Antarctic now, we won’t be able to make comparisons 10 or 20 years from now, so I think it is important that we do our research now.

    The consequences of earlier sea ice melting

    The northern Bering Sea, the gateway to the Arctic Ocean, is rich in plankton and is one of the world’s leading fishing grounds for snow crab, king crab, and cod. This area is usually covered by sea ice from December to April each year; however, in spring 2018, the sea ice melted about a month earlier than usual, affecting a wide range of organisms. In particular, fish and birds died, and worse nutritional status was reported. However, it was a mystery why such biological effects occur when sea ice melts earlier.

    We were able to unravel part of this mystery based on surveys in the northern Bering Sea carried out in 2017 and 2018 on the Oshoro Maru, a training vessel of the School of Fisheries Sciences at Hokkaido University. In 2018, when the sea ice melted earlier, there was a delay in the onset of the phytoplankton bloom—a massive increase in phytoplankton. Even if the sea ice melts earlier, the bloom is unlikely to occur at that time of year due to inadequate sunlight levels and the environment being more prone to mixing of seawater. As a result of the delayed bloom, it was found that zooplankton, which prey on phytoplankton, laid their eggs later, which also delayed their growth, resulting in smaller individuals. This affected the growth of fish and birds. We were able to clarify this because we were continuously collecting data on the Oshoro Maru. However, it is not yet known how these phenomena will affect the following year and beyond.

    Realizing how small your world is

    I have been interested in biology and environmental issues since I was in high school, but it wasn’t until I entered the fisheries department at university that I became interested in marine plankton. For example, I was surprised to see a plankton that is less than a millimeter long but has 20 legs, and I guess you could call it ‘biological beauty’, a very reasonable and functional form. The forms of living organisms all have meaning. The more research I do, the more I realize that all forms of living organisms have meaning, which I really enjoy. At the same time, as a researcher, I want to take as neutral a view of things as possible and be a voice for plankton and nature.

    Looking back on it now, I would like young people to get out and about. If you are interested in something, immerse yourself in it and actively communicate with seniors and researchers who are active in that field. This will make you feel closer to the world of experts, and conversely, you will realize how small your own world is. Through these experiences, I think you can also discover what you really like and what you want to do. Even if this is not connected to work, I think it will enrich your life.

    Column: The joys of fieldwork

    I like fieldwork—where I do research in the field. I enjoy the unexpected discoveries I make when I look at the plankton there, and the fact that these discoveries become the seeds for my next research project. But the preparation is hard work. Once you leave the port by boat, you have to make do with what you already have on board for two months, so I really think preparation is everything. Once we get there, we spend almost every waking moment sampling. That’s part of the fun.

    In addition, researchers from many different fields live and work together on the ship, so many ideas are born from such interactions and joint research can begin. The oceans are connected all over the world, so we cannot have closed discussions. Researchers from different countries can also conduct research together and put data together to get a fuller picture.

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  • Modeling ocean to understand natural phenomena

    Modeling ocean to understand natural phenomena

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    BYLINE: Space Time Inc.

    Newswise — Associate Professor Yoshi N. Sasaki, a specialist in Physical Oceanography, is involved in research into rising sea levels—particularly in coastal areas of Japan. He spoke about what he has learned so far about the relationship between ocean currents, sea level and climate change, what research he is currently focusing on, and the appeal of research that uses numerical modeling to uncover natural phenomena.

    Understanding future changes in sea level

    It is a common view among researchers that the global mean sea level is rising. The only question now is, by how much will it rise?

    The graph below shows global average sea level, with tide-gauge data since 1880 and satellite data since 1993. It shows that the water level rose at a rate of about 1.5 to 2 millimeters per year in the 20th century, but has increased at a faster rate of about 3 millimeters per year in the 21st century. This speed is expected to increase further in the future as global warming continues.

    Indeed, on the US coast, for example in Florida, many people live on low land, and sea levels are rising faster than in other areas of the ocean. In such areas, dike building and migration are already being considered.

    Researchers are now focusing on detailed predictions of what will cause sea level changes, when, in which areas, and to what extent.

    As this graph is a ‘global average,’ the actual situation at different locations is much more nuanced than this alone reveals. To clarify this, simulations using numerical models are being carried out.

    Sea level is the sum of multiple factors

    Sea level rise does not occur uniformly across the globe, but varies greatly from one ocean region to another. The causes also vary between global changes and changes in some ocean regions.

    There are two main causes of sea level rise on average across the globe. The first is the thermal expansion of seawater due to warming caused by global warming. The second is the melting of glaciers and ice sheets due to global warming. Water that was previously trapped on land as ice flows into the sea, increasing the mass of seawater and causing sea levels to rise.

    There are many different mechanisms by which sea level changes in different ocean regions. To give a few examples: one, variations in ocean circulation. Due to the physics of geostrophic currents, the sea level in the Northern Hemisphere is higher on the right side and lower on the left side in relation to the direction of the ocean currents. Two, changes in atmospheric pressure. Three, changes in the ground—the ground also sinks and rises, which changes the height of the coastal water table.

    In other words, to predict sea level in an area, a combination of these factors needs to be taken into account. Specifically, the effects of each of these factors can be added together to estimate the actual rise in sea level, to some extent.

    Understanding natural mechanisms using numerical models

    My research involves computer simulations, using regional ocean models of the US. In principle, the model can reproduce the state of the ocean by feeding it with observed data such as atmospheric winds and temperatures.

    For example, if we know that a change in water levels is caused by wind fluctuations, we can make predictions of future changes in water levels by knowing what the winds will be like in the future.

    Although I simply said ‘By wind fluctuations,’ it is about understanding the mechanisms of nature. For me, it’s something very enjoyable that satisfies my intellectual curiosity.

    Naturally, it is not a straightforward process. Models are very complex, and to understand the mechanism, the model must first be able to reproduce the phenomena accurately. Once that is done, a ‘simpler model’ that reproduces the same situation can be developed, revealing new principles hidden in nature. We need to look at the results of the complex models to find the essence of what is important.

    When I was doing research in the US, I discovered a new mechanism that changed the ocean circulation. To someone outside the field, it would have looked like just a diagram, but after working on it for a very long time, it suddenly looked like important information that no one had ever seen before. This is the best part of research.

    Water level fluctuations along the coast of Japan

    Water levels along the Japanese coast are also currently rising, but it is known that they did not rise all the way through the 20th century—they peaked once around 1950 and then fell.

    Our research has shown that the peak around 1950 was dominated by wind effects. In particular, it seems to have been caused by fluctuations in ocean circulation due to wind fluctuations from a low-pressure system called the Aleutian Low. On the other hand, the rise in recent years has been found to be primarily due to the effects of heat and other factors at the sea surface.

    Assessing the impact of typhoons and storm surges

    In the future, typhoons and extratropical cyclones are predicted to become stronger. So far, research has been conducted on how sea level changes on long-term time scales of a decade or more, but the possibility that short-term fluctuations, such as storm surges, could cause major damage cannot be ignored.

    In order to assess such impacts, we need to know exactly how typhoons and extratropical cyclones will strengthen in the future, and how this will affect sea levels. I am currently working on this with young students, and we are hoping to get this project off the ground.

    Sea level rise is one aspect of the wider ocean

    Right now, the resolution of ocean models for global warming simulations is approximately 100 kilometers, and can be narrowed down to 10 kilometers at the finest. This may be sufficient for some ocean regions, but it is not sufficient at all for some topographies, so I would like to create more detailed models and incorporate methods such as statistics and machine learning to estimate.

    On the other hand, there is also a conflict between effective measures and the economic aspects. For example, in the US,there were very specific discussions about the cost of migration to avoid the influence of sea level rise and the cost of building dikes, and which is better. Once you know certain things, the rest is no longer in the field of science, but in the field of politics or in the field of society. It’s about how much accuracy society demands.

    I myself would like to go back to the theme of ocean currents and look for more interesting and important phenomena caused by ocean currents once I have gone through sea level rise. I think there are still many interesting phenomena caused by ocean currents, such as ocean circulation. My dream for the future is to elucidate the mechanisms of these phenomena.

    Friendships gained in Hawaii

    After completing my doctoral studies at Hokkaido University, I chose a post-doctoral research fellowship at the University of Hawai’i in the US as my first job. The University of Hawai’i was one of the world’s strongest universities in marine research, but it was a big decision for me to do research abroad where Japanese was not spoken. It was a tough decision for me, as I was so committed to my research that I felt that if I did not achieve good results in Hawai’i, I would not be able to return to Japan. But it was very rewarding. As well as research, Hawai’i is a tourist destination, so a lot of researchers come here as visitors. I made a lot of acquaintances and connections in this environment, and it still helps me to build an international network.

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  • Nematodes joy ride across electric voltages

    Nematodes joy ride across electric voltages

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    Newswise — Hokkaido University researchers found that tiny nematode worm larvae surf electric fields to hitch rides on passing insects.

    Many living organisms are known to make use of electric fields. Some fish species use them to detect predators or prey, and insects such as bees use them to attract pollen while foraging. Now, a research group including scientists from Hokkaido University has discovered that juvenile nematode worms can surf electric fields to leap through the air and hitch a ride on passing insects. Their findings have been published in the journal Current Biology.

    Nematodes are one of many species that rely on larger animals to help them travel and disperse, an interaction called phoresy. They have been observed lifting themselves up on the tips of their tails (nictation), thus reducing their surface connection, to make it easier to attach themselves to a passing organism.

    To explore how they achieve this, the research team bred the nematode worm Caenorhabditis elegans on dog food in a petri dish. They noticed that the larvae of the nematode, called dauer larvae, consistently moved to the lid of the dish. Some of the larvae reached the lid by crawling up the side of the dish, and others appeared on the lid in a fraction of a second.

    “To more directly confirm the leap of C. elegans dauer larvae and to see how the worms leap in the dish and the characteristics of the leaping action, we observed a worm leaping in the Petri dish with a high-speed camera,” says Associate Professor Katsuhiko Sato at the Research Institute for Electronic Science, Hokkaido University, corresponding author of the study.

    This showed that the larvae kept its body quite straight before the leap, and a single dauer larvae engaged in this behavior could also carry several other larvae with it in a leap.

    The research team speculated that the nematode larvae might be using electrostatic forces to travel across the millimeters-wide gap between the substrate and the lid of the petri dish. They set up an experiment using a petri dish filled with agar and studded with tiny glass electrodes, with a separate glass electrode set up parallel to it. The larvae were placed on the agar, and the researchers applied different voltages to the two sets of electrodes to see how the larvae would behave.

    When no electric charge was applied, the larvae did not leap. But when an electric field above a certain voltage was applied, the nematodes leapt from one electrode to another at an average speed just under one meter per second.

    They then performed a second experiment using the bumblebee Bombus terrestris, which is known to use electrostatic charge to help it collect pollen, and saw the same leaping behavior when the bumblebee came with one to two millimeters of the nematode larvae.

    “Although C. elegans has not been reported to attach to bees, it is known to attach to flying insects such as moths and flies in the wild,” Sato notes. “We assume that C. elegans uses electric interactions to attach to insects, including bumblebees, in the wild.”

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  • Combination therapy effective against canine melanoma

    Combination therapy effective against canine melanoma

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    Newswise — A combination of radiotherapy followed by immunotherapy is a promising strategy for the treatment of oral malignant melanomas in dogs.

    Melanomas are the most common oral cancers in dogs. It is highly metastatic and conventional chemotherapy does not increase survival time. Canine oral melanomas are similar to human melanomas; thus, research is being conducted into adapting treatments developed for human melanomas for dogs.

    A particularly effective therapy for treating human melanomas is a combination of immune checkpoint inhibitors and radiotherapy. A team of researchers led by Professor Satoru Konnai at Hokkaido University has investigated the effects of this therapy in dogs. Their findings were published in the journal Cancers.

    “One of the means that tumors employ to protect themselves is by inducing overexpression of molecules that suppress the immune response, such as PD-1 and PD-L1,” explained Konnai. “Immunotherapy that targets these molecules and blocks their function has a response rate of 14.3% for canine oral malignant melanoma (OMM). Studies in humans have shown that combining anti-PD-L1 immunotherapy with radiotherapy—where the radiation is focused on the tumor—increases survival in humans, and we wanted to examine if this was true in dogs as well.”

    The team analyzed data from 39 canine patients with Stage IV pulmonary OMM treated with the anti-PD-L1 antibody c4G12 between March 2016 and September 2021. Of these, twenty had either never been treated with radiotherapy or had not received such treatment for at least 8 weeks; nine had received radiotherapy within 8 weeks prior to c4G12 treatment; and the remaining ten received c4G12 and radiotherapy concurrently.

    The most important metric the team measured was the overall survival time, the duration between the first dose of c4G12 and death. “The group that had received radiotherapy prior to c4G12 had better overall survival compared to the group that received just c4G12,” Konnai elaborated. “Concurrent treatment had no benefits compared to prior radiotherapy. We also observed that there was no statistical difference between the three groups in terms of side effects from treatment.” 

    This study shows that sequential treatment of canine pulmonary OMM with radiotherapy followed by c4G12 is a promising antitumor strategy. Future work will need to examine the validity of these findings in larger sample sizes, and will also focus on pinning down the optimal protocol (combination of timing, dose and fractionation of radiotherapy) to increase overall survival.

    Funding:
    This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (16K15042, 19H03114, 19K15969, 19K23702, 21K1498301) and Grant-in-Aid for JSPS Fellows (15J01989); and by the Japan Agency for Medical Research and Development (AMED; JP22ama121008, JP21am0101078).

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  • A common metabolite may help treat autoimmune diseases

    A common metabolite may help treat autoimmune diseases

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    Newswise — Researchers have revealed the modulatory effect of the anti-inflammatory metabolite itaconate on T helper and T regulatory cells, which may lead to new therapeutic approaches to treating some autoimmune diseases.

    Autoimmune diseases occur when the immune system attacks its own body. There are more than eighty known types of autoimmune diseases. In many cases, autoimmune diseases can be treated by suppressing the immune system; however, a side effect of such treatment is that the patient has an increased risk of severe infectious diseases, which is a leading cause of death. Hence there is a need to establish novel therapies for autoimmune diseases to reduce the risk of infectious diseases. 

    A research team led by Professor Tatsuya Atsumi, Assistant Professor Michihito Kono and graduate student Kuniyuki Aso at Hokkaido University, along with Senior Lecturer Masatoshi Kanda at Sapporo Medical University, has studied the effect of the molecule itaconate on the immune system. Their findings, which have implications for treating autoimmune disorders, were published in the journal Nature Communications.

    “Multiple sclerosis (MS) and systemic lupus erythematosus are two of the many autoimmune diseases caused by a dysregulation of T cells,” Kono explained. “We were interested in two types of T cells: T helper 17 (Th17) and regulatory T (Treg) cells. These cells have the same origin but have opposite functions in autoimmune diseases, and cell metabolites modulate their action. The metabolite we focused on was itaconate (ITA), as it has been shown to have anti-inflammatory, antiviral, and antimicrobial effects.”

    The researchers showed that, in cell cultures, ITA inhibited the differentiation of Th17 cells which have the potential to elaborate autoimmune diseases, and promoted that of Treg cells, which can ameliorate them. Further, in mice models with experimental autoimmune encephalomyelitis, ITA reduced the disease symptoms. Further tests were conducted to confirm that this effect was due to its effect on T cells.

    Investigations into the mechanism of action of ITA revealed that it inhibits essential metabolic pathways, glycolysis, oxidative phosphorylation, and methionine metabolism in Th17 and Treg cells. “ITA inhibits these pathways by directly inhibiting the enzymes methionine adenosyltransferase and isocitrate dehydrogenase, resulting in change of S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and 2-hydroxyglutarate levels,” Kono elaborated. “The altered cell metabolites also indirectly affect the chromatin accessibility of essential transcription factors and the synthesis of proteins required for the differentiation of Th17 and Treg cells.”

    “Our results explain the mechanisms that underlie the modulation of T cell differentiation,” he concluded. “This could eventually lead to simple therapeutic approaches which regulate T cell differentiation, thereby treating T cell-mediated autoimmune diseases.”

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  • Good and bad feelings for brain stem serotonin

    Good and bad feelings for brain stem serotonin

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    Newswise — New insights into the opposing actions of serotonin-producing nerve fibres in mice could lead to drugs for treating addictions and major depression.

    Scientists in Japan have identified a nerve pathway involved in the processing of rewarding and distressing stimuli and situations in mice. 

    The new pathway, originating in a bundle of brain stem nerve fibres called the median raphe nucleus, acts in opposition to a previously identified reward/aversion pathway that originates in the nearby dorsal raphe nucleus. The findings, published by scientists at Hokkaido University and Kyoto University with their colleagues in the journal Nature Communications, could have implications for developing drug treatments for various mental disorders, including addictions and major depression.

    Previous studies had already revealed that activating serotonin-producing nerve fibres from the dorsal raphe nucleus in the brain stem of mice leads to the pleasurable feeling associated with reward. However, selective serotonin reuptake inhibitors (SSRIs), antidepressant drugs that increase serotonin levels in the brain, fail to exert clear feelings of reward and to treat the loss of ability to feel pleasure associated with depression. This suggests that there are other serotonin-producing nerve pathways in the brain associated with the feelings of reward and aversion.

    To further study the reward and aversion nerve pathways of the brain, Hokkaido University neuropharmacologist Yu Ohmura and Kyoto University pharmacologist Kazuki Nagayasu, together with colleagues at several universities in Japan, focused their attention on the median raphe nucleus. This region has not received as much research attention as its brain stem neighbour, the dorsal raphe nucleus, even though it also is a source of serotonergic nerve fibres.

    The scientists conducted a wide variety of tests to measure activity of serotonin neurons in mice, in response to stimulating and inhibiting the median raphe, by using fluorescent proteins that detect entry of calcium ions, a proxy of neuronal activation in a cell-type specific manner.

    They found that, for example, pinching a mouse’s tail—an unpleasant stimulus—increased calcium-dependent fluorescence in the serotonin neurons of the median raphe. Giving mice a treat such as sugar, on the other hand, reduced median raphe serotonin fluorescence. Also, directly stimulating or inhibiting the median raphe nucleus, using a genetic technique involving light, led to aversive or reward-seeking behaviours, such as avoiding or wanting to stay in a chamber—depending on the type of stimulus applied.

    The team also conducted tests to discover where the switched-on serotonergic nerve fibres of the median raphe were sending signals to and found an important connection with the brain stem’s interpenduncular nucleus. They also identified serotonin receptors within this nucleus that were involved in the aversive properties associated with median raphe serotonergic activity.

    Further research is needed to fully elucidate this pathway and others related to rewarding and aversive feelings and behaviours. “These new insights could lead to a better understanding of the biological basis of mental disorders where aberrant processing of rewards and aversive information occur, such as in drug addiction and major depressive disorder,” says Ohmura.

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