Bravery cells found in the hippocampus

Press Releases   •   Sep 07, 2018 10:00 BST

Why do some people comfortably walk between skyscrapers on a high-wire or raft the Niagara Falls in a wooden barrel whereas others freeze on the mere thought of climbing off escalators in a shopping mall? In a new study, scientists have found that a certain type of cells in the hippocampus play a key role.

People are very different when it comes to trying dangerous or exhilarating things. Even siblings can show dramatic differences in risk-taking behaviour. The neural mechanisms that drive risk-taking behaviour are largely unknown. However, scientists from the Department of Neuroscience of Uppsala University in Sweden and the Brain Institute of the Federal University of Rio Grande do Norte in Brazil have found that some cells in the hippocampus play a key role in risk taking behaviour and anxiety.

In an article published in the journal Nature Communications the authors show that neurons known as OLM cells, when stimulated, produce a brain rhythm that is present when animals feel safe in a threatening environment (for example, when they are hiding from a predator but aware of the predator's proximity). The study, produced by Drs. Sanja Mikulovic, Ernesto Restrepo, Klas Kullander and Richardson Leao among others, showed that anxiety and risk-taking behaviour can be controlled by the manipulation of OLM cells. To find a pathway that quickly and robustly modulates risk-taking behaviour is very important for treatment of pathological anxiety since reduced risk-taking behaviour is a trait in people with high anxiety levels.

Adaptive (or normal) anxiety is essential for survival because it protects us from harm. Unfortunately, in a large number of people, anxiety can be dysfunctional and severely interfere with daily life. In these cases, doctors often rely on antidepressants to help patients recover from the dysfunctional state. However, these drugs act in the entire brain and not only in the areas where it is needed and may therefore have severe side-effects. Thus, to act in a single brain region and in a very specific group of cells to control anxiety may be a major breakthrough in treating anxiety and associated disorders like depression. Another interesting finding in the study is that OLM cells can also be controlled by pharmacological agents. In the past, the same group of scientists have found that OLM cells were the ‘gatekeepers’ of memories in the hippocampus and that these cells were very sensitive to nicotine.

‘This finding may explain why people binge-smoke when they are anxious’, says Dr. Richardson Leao, researcher at the Brain Institute of the Federal University of Rio Grande do Norte and Uppsala University.

The participation of the hippocampus in emotions is much less studied than its role in memory and cognition. In 2014, for example, the Nobel prize was awarded for the discovery of “place cells” that represent a biological GPS and underlie the memories of where we are located in our surroundings. In the past decade, scientists have started to appreciate the role of the hippocampus also in regulating emotions.

‘It is fascinating how different regions of the same brain structure control distinct behaviours and how they interact with each other. Identifying specific circuits that underlie either cognitive or emotional processes is crucial for the general understanding of brain function and for more specific drug development to treat disorders’, says Dr. Sanja Mikulovic, Uppsala University.

The discovery of these neurons and their role in anxiety and risk-taking may open a path for the development of highly efficient anxiolytics and antidepressants without common side-effects, such as apathy.

For more information, please contact:

Klas Kullander, Professor at the Department of Neuroscience, Uppsala University tel: + 46 18-471 45 19, + 46 70-846 7524, email: klas.kullander@neuro.uu.se
Richardson Leao, Research Assistant, Department of Neuroscience, Uppsala University, email: Richardson.Leao@neuro.uu.se

Ventral hippocampal OLM cells control type 2 theta oscillations and response to predator odor, Nature Communications, DOI: 10.1038/s41467-018-05907-w

Uppsala University -- quality, knowledge, and creativity since 1477
World-class research and outstanding education of global benefit to society, business, and culture.
Uppsala University is one of northern Europe's highest ranked academic institutions. www.uu.se

Why do some people comfortably walk between skyscrapers on a high-wire or raft the Niagara Falls in a wooden barrel whereas others freeze on the mere thought of climbing off escalators in a shopping mall? In a new study, scientists have found that a certain type of cells in the hippocampus play a key role.

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How sleep loss may contribute to adverse weight gain

Press Releases   •   Aug 23, 2018 08:43 BST

In a new study, researchers at Uppsala University now demonstrate that one night of sleep loss has a tissue-specific impact on the regulation of gene expression and metabolism in humans. This may explain how shift work and chronic sleep loss impairs our metabolism and adversely affects our body composition. The study is published in the scientific journal Science Advances.

Epidemiological studies have shown that the risk for obesity and type 2 diabetes is elevated in those who suffer from chronic sleep loss or who carry out shift work. Other studies have shown an association between disrupted sleep and adverse weight gain, in which fat accumulation is increased at the same time as the muscle mass is reduced – a combination that in and of itself has been associated with numerous adverse health consequences. Researchers from Uppsala and other groups have in earlier studies shown that metabolic functions that are regulated by e.g. skeletal muscle and adipose tissue are adversely affected by disrupted sleep and circadian rhythms. However, until now it has remained unknown whether sleep loss per se can cause molecular changes at the tissue level that can confer an increased risk of adverse weight gain.

In the new study, the researchers studied 15 healthy normal-weight individuals who participated in two in-lab sessions in which activity and meal patterns were highly standardised. In randomised order, the participants slept a normal night of sleep (over eight hours) during one session, and were instead kept awake the entire night during the other session. The morning after each night-time intervention, small tissue samples (biopsies) were taken from the participants’ subcutaneous fat and skeletal muscle. These two tissues often exhibit disrupted metabolism in conditions such as obesity and diabetes. At the same time in the morning, blood samples were also taken to enable a comparison across tissue compartments of a number of metabolites. These metabolites comprise sugar molecules, as well as different fatty and amino acids.

The tissue samples were used for multiple molecular analyses, which first of all revealed that the sleep loss condition resulted in a tissue-specific change in DNA methylation, one form of mechanism that regulates gene expression. DNA methylation is a so-called epigenetic modification that is involved in regulating how the genes of each cell in the body are turned on or off, and is impacted by both hereditary as well as environmental factors, such as physical exercise.

“Our research group were the first to demonstrate that acute sleep loss in and of itself results in epigenetic changes in the so-called clock genes that within each tissue regulate its circadian rhythm. Our new findings indicate that sleep loss causes tissue-specific changes to the degree of DNA methylation in genes spread throughout the human genome. Our parallel analysis of both muscle and adipose tissue further enabled us to reveal that DNA methylation is not regulated similarly in these tissues in response to acute sleep loss,” says Jonathan Cedernaes who led the study.

“It is interesting that we saw changes in DNA methylation only in adipose tissue, and specifically for genes that have also been shown to be altered at the DNA methylation level in metabolic conditions such as obesity and type 2 diabetes. Epigenetic modifications are thought to be able to confer a sort of metabolic “memory” that can regulate how metabolic programmes operate over longer time periods. We therefore think that the changes we have observed in our new study can constitute another piece of the puzzle of how chronic disruption of sleep and circadian rhythms may impact the risk of developing for example obesity,” notes Jonathan Cedernaes.

Further analyses of e.g. gene and protein expression demonstrated that the response as a result of wakefulness differed between skeletal muscle and adipose tissue. The researchers say that the period of wakefulness simulates the overnight wakefulness period of many shift workers assigned to nightwork. A possible explanation for why the two tissues respond in the observed manner could be that overnight wakefulness periods exert a tissue-specific effect on tissues’ circadian rhythm, resulting in misalignment between these rhythms. This is something that the researchers found preliminary support for also in this study, as well as in an earlier similar but smaller study.

“In the present study we observed molecular signatures of increased inflammation across tissues in response to sleep loss. However, we also saw specific molecular signatures that indicate that the adipose tissue is attempting to increase its capacity to store fat following sleep loss, whereas we instead observed signs indicating concomitant breakdown of skeletal muscle proteins in the skeletal muscle, in what’s also known as catabolism. We also noted changes in skeletal muscle levels of proteins involved handling blood glucose, and this could help explain why the participants’ glucose sensitivity was impaired following sleep loss. Taken together, these observations may provide at least partial mechanistic insight as to why chronic sleep loss and shift work can increase the risk of adverse weight gain as well as the risk of type 2 diabetes,” says Jonathan Cedernaes.

The researchers have only studied the effect of one night of sleep loss, and therefore do not know how other forms of sleep disruption of circadian misalignment would have affected the participants’ tissue metabolism.

“It will be interesting to investigate to what extent one or more nights of recovery sleep can normalise the metabolic changes that we observe at the tissue level as a result of sleep loss. Diet and exercise are factors that can also alter DNA methylation, and these factors can thus possibly be used to counteract adverse metabolic effects of sleep loss,” says Jonathan Cedernaes.


For more information, please contact:
Jonathan Cedernaes, M.D., Ph.D. at the Neuroscience Department, Uppsala University. Tel.: +1-312-866-0125, email: jonathan.cedernaes@neuro.uu.se

Cecilia Yates, Press information officer at the Neuroscience Department, Uppsala University. Tel.: +46 704 334 801, email: cecilia.yates@neuro.uu.se

Citation: Cedernaes et al. Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans. Science Advances. 2018;4:eaar8590. (in press)

The researchers are supported by among others AFA Försäkring, the Novo Nordisk Foundation, the Swedish SciLifeLab (e.g. WABI and the Swedish metabolomics center), the Swedish Brain Foundation, the Swedish Research Council, and the Åke Wiberg Foundation.

Uppsala University -- quality, knowledge, and creativity since 1477
World-class research and outstanding education of global benefit to society, business, and culture.
Uppsala University is one of northern Europe's highest ranked academic institutions. www.uu.se

In a new study, researchers at Uppsala University now demonstrate that one night of sleep loss has a tissue-specific impact on the regulation of gene expression and metabolism in humans. This may explain how shift work and chronic sleep loss impairs our metabolism and adversely affects our body composition. The study is published in the scientific journal Science Advances.

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Catastrophic floods can trigger human resettlement away from rivers

Press Releases   •   Aug 22, 2018 19:00 BST

A new study by researchers at Uppsala University, published in the journal Science Advances, uses satellite nighttime light data to reveal how flood protection shapes the average distance of settlements from rivers.

Flooding is one of the most damaging natural hazards, and its negative impacts have markedly increased in many regions of the world in recent decades. In the period 1980–2014, floods generated economic losses exceeding USD 1 trillion and caused more than 226,000 casualties. The increasing trend of global flood losses has mainly been attributed to the increasing exposure of people and assets due to rising populations in flood-prone areas.

To understand (spatiotemporal) changes in flood risk, one needs to determine the way in which humans adapt and respond to flood events. For example, societies can cope with floods by reinforcing structural flood protection, implementing early warning systems and building codes, or by moving away from flood-prone areas.

By using satellite nighttime light data, a group of researchers at Uppsala University has been able to discern the relationship between long-term changes in human proximity to rivers (that is, the average distance of human settlement from rivers) and the occurrence of catastrophic flood events, with reference to different levels of structural flood protection (for example, levees and reservoirs/dams). This type of analysis has not been feasible previously because traditional census data are typically aggregated at administrative levels and available on decadal time scales. Thus, census data do not provide useful information needed to explore these relationships.

By focusing on the occurrence of catastrophic flood events (inferred from flood damage) in 16 countries across the globe, with different hydroclimatic and socioeconomic contexts as well as different levels of structural flood protection, the research group found that flood fatalities and economic losses on the country scale are both positively correlated with changes in human proximity to rivers. However, such tendencies are reduced when high levels of flood protection are in place.

More detailed analysis in four hotspot areas confirms these tendencies. Catastrophic flood events may trigger changes in human proximity to rivers.

“We found that societies with low protection levels tend to resettle further away from the river after catastrophic flood events, and that the decrease in human settlements close to the river may have contributed to reduced exposure to future flood events. Conversely, societies with high protection levels show no significant changes in human proximity to rivers,” says Johanna Mård, researcher at the Department of Earth Sciences, Uppsala University.

Societies with high protection levels continue to rely heavily on structural measures, reinforcing flood protection and quickly resettling in flood-prone areas after a flooding event. Although they will be protected from frequent flooding, total protection is not possible, and therefore they remain exposed to low-probability but catastrophic-impact events.

The study reveals interesting aspects of human adaptation to flood risk and offers key insights for comparing different risk reduction strategies. The analysis indicates that flood occurrences can trigger decreasing human proximity to rivers but mainly if societies do not strongly rely on structural protective measures. In addition, this study provides a framework that can be used to further investigate human response to floods, which is relevant as the urbanisation of floodplains continues and puts more people and economic assets at risk.

For more information, please contact:

Johanna Mård, Researcher at the Department of Earth Sciences, Uppsala University, Uppsala, Sweden, johanna.maard@geo.uu.se +46 18 471 3095

Giuliano Di Baldassarre, Professor at the Department of Earth Sciences, Uppsala University, Uppsala, Sweden, Giuliano.dibaldassarre@geo.uu.se 

Johanna Mård, Giuliano Di Baldassarre and Maurizio Mazzoleni (2018) Nighttime light data reveal how flood protection shapes human proximity to rivers, Science Advances, DOI: 10.1126/sciadv.aar5779 

This work was supported by Formas and the European Research Council within the project HydroSocialExtremes led by Giuliano Di Baldassarre, Director of the Centre of Natural Hazards and Disaster Science (www.cnds.se).

Uppsala University -- quality, knowledge, and creativity since 1477
World-class research and outstanding education of global benefit to society, business, and culture.
Uppsala University is one of northern Europe's highest ranked academic institutions. www.uu.se

A new study by researchers at Uppsala University, published in the journal Science Advances, uses satellite nighttime light data to reveal how flood protection shapes the average distance of settlements from rivers.

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Working memory might be more flexible than previously thought

Press Releases   •   Aug 16, 2018 12:52 BST

Breaking with the long-held idea that working memory has fixed limits, a new study by researchers at Uppsala University and New York University suggests that these limits adapt themselves to the task that one is performing. The results are presented in the scientific journal eLife.

You can read this sentence from beginning to end without losing track of its meaning thanks to your working memory. This system temporarily stores information relevant to whatever task you are currently performing. However, the more objects you try to hold in working memory at once, the poorer the quality of each of the resulting memories.

It has long been argued that this phenomenon – known as the set size effect – occurs because the brain devotes a fixed amount of neural resources to working memory. But this theory struggles to account for certain experimental results. It also fails to explain why the brain would not simply recruit more resources whenever it has more objects to remember. After all, your heart does something similar by beating faster whenever you increase your physical activity.

Van den Berg and Ma break with the idea that working memory resources are fixed. Instead, they propose that resource allocation is flexible and driven by balancing between two conflicting goals: maximize memory performance, but use as few neural resources as necessary.

They turned this idea into a computational model and tested it on data from nine previously published experiments. In those experiments, human subjects memorized the colors of varying numbers of objects. When asked to reproduce these colors as precisely as possible, the quality of their responses was negatively affected by the number of objects in memory. The model by Van den Berg and Ma accurately mimics this set size effect in all nine datasets. Moreover, their model simulations predict that the objects most relevant for a task are stored more accurately than less important ones, a phenomenon also observed in participants. Lastly, their simulation predicts that the total amount of resources devoted to working memory varies with the number of objects to be remembered. This too is consistent with the results of previous experiments.

Working memory thus appears to be more flexible than previously thought. The amount of resources that the brain allocates to working memory is not fixed but could be the result of balancing resource cost against cognitive performance. If this is confirmed, it may be possible to improve working memory by offering rewards, or by increasing the perceived importance of a task.

For more information please contact: 

Ronald van den Berg, researcher at the Department of Psychology, Uppsala University: email: ronald.vandenberg@psyk.uu.se
telephone: + 46 18-471 7980 // +46 73 572 1727

Ronald van den Berg, Wei Ji Ma, A resource-rational theory of set size effects in human visual working memory, eLife 2018;7:e34963 doi: 10.7554/eLife.34963

Uppsala University -- quality, knowledge, and creativity since 1477
World-class research and outstanding education of global benefit to society, business, and culture.
Uppsala University is one of northern Europe's highest ranked academic institutions. www.uu.se

Breaking with the long-held idea that working memory has fixed limits, a new study by researchers at Uppsala University and New York University suggests that these limits adapt themselves to the task that one is performing. The results are presented in the scientific journal eLife.

Read more »

There is not one kind of “good sperm” – it depends on other qualities in the male

Press Releases   •   Aug 16, 2018 11:00 BST

In a study published in Behavioral Ecology researchers from Uppsala University show that the same type of sperm is not always the best for all male birds. Depending on how attractive or dominant you are you might be more successful with longer or shorter sperm.

Magnetic antiparticles offer new horizons for information technologies

Press Releases   •   Aug 15, 2018 14:04 BST

Nanosized magnetic particles called skyrmions are considered highly promising candidates for new data storage and information technologies. Now, physicists have revealed new behaviour involving the antiparticle equivalent of skyrmions in a ferromagnetic material. The results are published in Nature Electronics.

​The end-Cretaceous extinction unleashed modern shark diversity

Press Releases   •   Aug 02, 2018 17:00 BST

A study that examined the shape of hundreds of fossilized shark teeth suggests that modern shark biodiversity was triggered by the end-Cretaceous mass extinction event, about 66 million years ago. This finding is reported this week in Current Biology.

​Magma storage and eruptive behaviour at Bali volcano

Press Releases   •   Jul 16, 2018 13:37 BST

A new study by researchers at Uppsala University and INGV, Italy, sheds light on magma storage under the currently active Agung volcano on the island of Bali in Indonesia. Magma at Agung is stored at both mantle (~20 km) and shallow crustal (~5 km) depths, which may be a potential cause for sudden pressure-driven eruptions in this densely populated part of the world. (Scientific Reports 180712)

New research detects brain cell that improves learning

Press Releases   •   Jul 05, 2018 16:00 BST

The workings of memory and learning have yet to be clarified, especially at the neural circuitry level. But researchers at Uppsala University have now, jointly with Brazilian collaborators, discovered a specific brain neuron with a central role in learning. This study, published in Neuron, may have a bearing on the potential for counteracting memory loss in Alzheimer’s disease.

When a person with dementia forgets having just eaten dinner, it is due to hippocampus damage. In contrast, the same person can describe in vivid detail a fishing trip to Norway 40 years ago. Both cases entail the use of episodic memory, the brain’s storage of events in which we have been personally involved. Dementia diseases impair the ability to form new memories, especially of events since the onset of the disease.

Researchers at Uppsala University have now, jointly with Brazilian colleagues, found certain neurons in the brain that play a crucial part in learning. The same research group had previously discovered ‘gatekeeper cells’ or, in technical parlance, OLM (Oriens-lacunosum moleculare) cells. These are located in the hippocampus, the brain area known to be active in forming new memories. The new findings from Klas Kullander’s research group show that OLM cells’ activity affects the encoding of memories in the brain.

When the OLM cells were overactivated in experiments on laboratory mice, the mice’s memory and learning functions deteriorated. When these cells were inactivated instead, the function of new memory formation improved. This research has enhanced understanding of how a single component in the memory circuits can affect memory formation.

“We had expected to be able to impair learning, since it seemed likely that the effect of our experiment at the cellular level would disturb the normal function of the nervous system. However, we were surprised to find that learning and memory also could be improved,” says Klas Kullander.

It also offers hope of being able to counteract the loss of memory formation in Alzheimer’s disease and dementia. The first symptoms of Alzheimer’s, the most common and familiar dementia disease, are associated with poor memory. Short-term memory is particularly impaired. For those who suffer from dementia symptoms, losing memory functions is a major everyday problem. Unfortunately, there are no curative treatments or medicines that can stop dementia diseases from developing.

“The next step is therefore to investigate this more closely, in further experiments on animal subjects comparable to humans. We need more knowledge before experiments can be done to stimulate the OLM cell artificially in humans,” Kullander says.

Reference: OLMα2 cells bidirectionally modulate learning. Samer Siwani, Arthur S. C. França, Sanja Mikulovic, Amilcar Reis, Markus M. Hilscher, Steven J. Edwards, Richardson N. Leão, Adriano B. L. Tort, Klas Kullander. Neuron (in press). DOI: 10.1016/j.neuron.2018.06.022

Klas Kullander, Professor at the Department of Neuroscience, researches neuronal circuitries and their functions. His international research group studies neuronal circuitries that are important for learning, memory, motor skills and cognition. The studies are conducted using methods in genetics, molecular biology and electrophysiology.

The research has been carried out with support from the Swedish Research Council, the Swedish Brain Foundation (Hjärnfonden) and the Bissen Brainwalk charitable event.

For more information, contact Professor Klas Kullander. Tel.: +46 18 471 4519, +46 70 846 7524, email klas.kullander@neuro.uu.se.

Uppsala University -- quality, knowledge, and creativity since 1477
World-class research and outstanding education of global benefit to society, business, and culture.
Uppsala University is one of northern Europe's highest ranked academic institutions. www.uu.se

The workings of memory and learning have yet to be clarified, especially at the neural circuitry level. But researchers at Uppsala University have now, jointly with Brazilian collaborators, discovered a specific brain neuron with a central role in learning. This study, published in Neuron, may have a bearing on the potential for counteracting memory loss in Alzheimer’s disease.

Read more »

Striking differences in brain morphology between wild and domestic rabbits

Press Releases   •   Jun 25, 2018 20:00 BST

The most characteristic feature of domestic animals is their tame behaviour. A team of scientists has now used high-resolution magnetic resonance imaging (MRI) to study how domestication has affected brain morphology in domestic rabbits. The results show that domestication has had a profound effect on brain morphology in particular regions of the brain involved in fear processing.

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