Eine Landkarte im Gehirn

Edvard Moser fand ihn unter seinen entgangenen Anrufen: den Anruf des Stockholmer Nobelpreiskommitees. Erst als er in München aus dem Flugzeug stieg, erfuhr der norwegische Forscher, dass er einer der Nobelpreisträger 2014 für Physiologie sei. Gemeinsam mit seiner Ehefrau und Ko-Gruppenleiterin May-Britt Moser und dem britisch-amerikanischen Forscher John O’Keefe, bei dem die Mosers eine kurze Zeit lang forschten, erhält er den Nobelpreis für die Entdeckung der “Landkarte im Gehirn”.

Bereits 1971 entdeckte John O’Keefe Nervenzellen, die Ratten als Kompass dienen. Er taufte sie “Platzzellen” (englisch: place cells). Läuft die Ratte durch den Käfig, sendet eine Platzzelle ein Signal, wenn die Ratte beim Futterspender steht, während eine andere Platzzelle sendet, wenn die Ratte in der hinteren Käfigecke hockt. Eine Platzzelle feuert also immer dann ein Signal ab, wenn sich die Ratte an einem bestimmten Punkt befindet. An jedem Ort feuert nur eine geringe Zahl an Platzzellen, die sich in einer speziellen Hirnregion, dem Hippocampus, befinden. So kodieren die Signale von nur wenigen Nervenzellen jeden Punkt in der Umgebung.

Nur eine Schaltstelle zwischen Nervenzellen, Synapse genannt, trennt Platzzellen und “Koordinaten-Zellen”. Zwischen der Entdeckung von Platzzellen durch John O’Keefe und der ersten Beschreibung von Koordinaten-Zellen (englisch: grid cells) durch May-Britt und Edvard Moser verstrichen aber über 30 Jahre. 2005 entdeckten die beiden Norweger ein Koordinatensystem im Gehirn von Ratten. Sie zeichneten dafür, ähnlich wie O’Keefe, die Signale auf, die Nervenzellen senden. Anders als O’Keefe konzentrierten sie sich auf Signale von Nervenzellen im sogenannten entorhinalen Kortex. Das “Feuern” von Nervenzellen klingt beim Aufzeichnen wie das Poppen von Popcorn in der Mikrowelle: jedes Signal ist ein “Pop”. Wenn eine Ratte durch eine experimentelle Umgebung läuft, das ist meistens einfach eine Kiste, hörten die Forscher immer wieder ein Pop. An manchen Orten aber “poppte” es ganz besonders häufig, wie wenn das meiste Popcorn im Sackerl aufspringt.

Zeichnen wir an jedem Ort, an dem sich die Ratte befindet, wenn eine Koordinatenzelle am meisten “poppt”, einen Punkt, entsteht rasch ein faszinierendes Muster: die “Pops” konzentrieren sich auf Sechsecke, die sich in regelmäßigen Abständen wiederholen. Alle Koordinatenzellen feuern in diesem sechseckigen Muster. Bei manchen Koordinatenzellen sind die Sechsecke aber größer oder kleiner, nach links oder rechts verdreht, oder näher oder weiter von einander entfernt. Dieses Koordinatensystem legt sich über den ganzen Raum der Ratte: wie der Längen- und Breitengrad jeden Ort der Welt bestimmen, definieren eine Handvoll Koordinatenzellen jeden Punkt in der Umgebung der Ratte.

Ratten haben noch mehr Nervenzellen, die nur an bestimmten Orten oder Positionen Signale senden: “Kopfrichtungszellen” feuern, wenn die Ratte den Kopf in eine bestimmte Himmelsrichtung hält, “Grenzzellen” senden Signale, wenn die Ratte in einem bestimmten Abstand von einer Wand läuft. Platzzellen und Koordinatenzellen bilden, zusammen mit den Kopfrichtungszellen und Grenzzellen, eine “Landkarte” im Gehirn der Ratte. Mit dieser Landkarte hat die Ratte auch im Dunkeln und in einer neuen Umgebung immer eine Darstellung davon, wo sie ist und wohin sie sich bewegt.

Ein ähnliches GPS befindet sich vermutlich auch in unserem menschlichen Gehirn. Edvard Mosers Platzzellen und Koordinatenzellen, die gerade feuerten, als er von seinem Nobelpreis erfuhr, sind wahrscheinlich untrennbar mit Freude verbunden.

Paper von John O’Keefe und Jonathan Dostrovsky:

Paper von May-Britt Moser und Edvard Moser

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Cognitive research – coming to a smartphone near you

“Citizen science” projects have successfully gotten people to classify galaxy shapes, find optimal protein folding structures or decipher manuscripts. But is it possible to use online participation not just to harness users problem-solving abilities but for actual experiments and data gathering in cognitive research? There has been much furore recently about a study on the spread of emotion that used data not only gathered through Facebook without users’ consent, but for which users’ newsfeed was actively manipulated. In contrast, researchers from the University of Oxford and the University of Birmingham now show that data for cognitive science experiments can be crowdsourced with informed consent, and results from the mass data collection replicate results which researchers got when they carried out experiments with the same aim in a carefully controlled lab setting.

The researchers got an app produced for smartphones, which allows users to play four short games that are based on classic experimental paradigms of cognitive science. These tested decision-making, short-term memory, perception and action inhibition but were packaged as competitive games. In one of them, users tapped their screen when fruit fell from a tree, but not when the fruit turned brown while falling. When the users tapped correctly and quickly enough, they progressed to the next level, where fruits turned brown later in their fall. Before playing, users filled out a questionnaire about themselves and gave informed consent for the use of their data. Interestingly, when analyzing the data, the researchers got the same results that other researchers got when they carried out experiments with the same goal in a lab setting, with only a few participants. One advantage of mass data collection over the internet is that the participants come from a wider demographic than the usual lab rats for cognitive science, cash-strapped university students. Soon, there will be two billion people using smartphones worldwide. That’s quite a wide pool of potential participants for online experiments, if done correctly. And, Facebook – no, informed consent is not optional.

Original research paper in PLOS One

Good vibrations?

“Fit in 15 minutes” – just 15 minutes training to get the same results as in a one and a half hours of sweaty workouts – that’s one of the promises of the “vibroplate”, “powerplate” and similar gyms promoting doing exercises on a vibrating plate. “Clever in 15 minutes” might be another claim they are making soon. Researchers in the Netherlands tested whether sitting on a vibrating plate could improve cognition in young, healthy adults. We know that exercise can improve memory, reasoning and problem solving, so-called “executive functions”. However, how can people who are unable to physically exercise reap the same benefits? The researchers tested whether passively sitting on a chair mounted on a vibrating platform – called whole body vibration – could improve executive functions. They found that after two minutes of such whole body vibration, volunteers performed better on a color-word interference test. In this test, participants are shown cards with 20 color names, each printed in one of five colors. However, the ink color of each word is different from the color name. The participants are asked to name the ink color of the word as fast as possible. In the study, participants were quicker in naming the correct ink colors after vibration. But they only improved if they took this test, designed to measure attention and inhibition, immediately after the end of vibrations. They did not improve if another two-minute test, measuring working memory, was done in between. And they also did not score any better on the working memory test.

The researchers suggest that vibrations might stimulate skin receptors that respond to vibrations. They send signals to a region of the brain strongly connected to the prefrontal cortex, which is involved in cognition and the processing of information. However, it is yet to early to add “become Einstein in 15 minutes” to the claims of vibration gyms. The observed improvement only lasts for a short while, less than a minute and only for a specific type of cognition, attention. And the researchers themselves suggest that it is necessary to test how long the vibration sessions have to be, and how often they have to be repeated, to see any strong effects on cognition. But in the long run, whole body vibration might turn out to be clinically relevant, and help people unable to exercise to at least have some of the benefits of going to the gym. For everyone else, the best reason to go to the gym in the meantime probably remains to simply get fit.

Original research paper in PLOS One

Is Alzheimer’s a prion disease?

Alzheimer’s disease affects more than 30 million people worldwide. One cause of this devastating type of dementia are tangles of a protein called tau. Tau usually binds to the cell’s inner skeleton, but in patients it groups together in brain cells and forms tangles, clogging them up. Other neurodegenerative diseases are also caused by tau, together they are called “diseases of tau” or tauopathies. Already 30 years ago, some researchers suggested that the cause for Alzheimer’s and other tauopathies could be a mechanism similar to prions – of mad cow disease fame. Prion-diseases like mad cow, Creuzfeldt-Jakob or scrapie are caused by small prion proteins that clump together. Prions come in different strains, which each cause different forms of clumps. Such clumps are “seeded”: one prion folds into an abnormal structure and causes other, normal, prions to also deform and clump together. Alzheimer’s and other tauopathies spread through networks of brain cells. This suggest that something toxic moves from one brain cell to the next, for example tangles of tau. Also a prion-like process of “seeding” has been suggested, with a tau tangle causing normal tau to deform . But conclusive proof of Alzheimer’s being a prion disease has been missing so far. In a paper in press in Neuron, researchers from the US and the UK show that tau acts like a prion.

Tau in a normal cell, and the formation of bundles in a cell of an Alzheimer's disease patient. Copyright: NIH

Tau in a normal cell, and the formation of bundles in a cell of an Alzheimer’s disease patient. Copyright: NIH

Scientists define prion diseases as “strains” of clumps that transmit into a cell or organism, can be extracted from a cell or organism and then when put back into a new cell or organism cause the same structure of clumps. In their work, the papers’ authors seek to show that a similar process is at work in Alzheimer’s disease. As the brain is a complex organ, scientists often use cells grown in a dish, in so-called cell culture, as a first start in their study. Here, the researchers made cells that produce a tau protein that glows yellow, but otherwise folds normally. When they added small tangles of tau into the cells, the yellow tau protein also joined the tangles. They then isolated colonies of cells with tangles, called clones, and allowed them to grow in single dishes. Different clones had different properties of tau tangles, like the size or position of tangles in the cell. The researchers then burst open clone cells, and put the cell solution into a dish with fresh cells with normal tau. The normal cells then form tau tangles, with the same properties as the clone used to infect them. These tau clones behave similar to prion strains, and the researchers call them tau strains.

The researchers then moved on to look at tau tangles in mouse brains. When they put cell solution into the brain of mice, the different strains cause differing tangle types in different neuron groups. Brain solution from mice infected with one strain caused newly infected mice to get the same tangle structure in the same neuron groups. When the researchers put tau tangles into a brain region called the hippocampus, tangles spread to regions whose brain cells project to or from the hippocampus. This shows that tau tangles spread from one brain region to others that are connected with it by their cells. Finally, when the researchers isolate tau tangles from mice and put them back into cells, they get back the same strain specific tangle structure they started out with.

As a final indicator of whether tau behaves like a prion, the researchers looked at different human tauopathies. For this, they used brain extracts from donated brains of patients who suffered from five different tauopathies, including Alzheimer’s. When extracts from different diseases are put into cells, different and distinct tangle types form. Different tauopathies with their specific disease characteristics are therefore caused by different strains of tau tangles.

For all intents and purposes, from this paper, it looks like tau behaves and is a prion. Strains can be extracted, form distinct clump types, and different strains cause different types of diseases. One important difference that sets Alzheimer’s apart from classic prion diseases like mad cow disease and scrapie is that Alzheimer’s is not infectious , and spreads only within an individual. The paper’s authors posit, however, that limiting the term prion to mean only infectious particles could artificially limit our view of prion diseases, and ignore a mechanism that unites a range of diseases. Also, over 95 percent of human prion disease cases appear to be genetic or spontaneous (sporadic) anyways, and are not linked to an infection, nevertheless they are seen as a prion disease. Does this have any implications for the treatment of Alzheimer’s and other tauopathies? Seen as there is currently no treatment for prion diseases, it might not seem so. But the observation that tau tangles spread from one neuron to the next gives a glimmer of hope. When tau spreads, it is briefly outside of the neuron. In the space outside the neuron, tau is exposed to potential new therapeutics, for example to prevent tangle spread, or to contain the infectious tau tangle in only a limited area of the brain. This paper puts the hypothesis that tau is a prion on firmer ground, and could be a step in the direction of developing a cure for Alzheimer’s – even if only by pointing out one potential angle of attack.

The original research appeared in Neuron: http://www.cell.com/neuron/abstract/S0896-6273%2814%2900362-6

sperm spirals to its goal

When you’re trying to get pregnant, after a while, cuddling afterwards will inevitably be replaced by the charming beetle pose – lying on your back, legs up in the air. All in the hope of getting the little swimmers on their way to their goal. On their journey through the cervix, uterus and the oviduct they cover a route thousand times longer than the length of a sperm cell. Also, while sperm might travel along in a current of fluid in the cervix and uterus, in the oviduct mucus flows in the opposite direction to the sperms itinerary. How sperm manages to stay on track and not stray is not known, but understanding this process would help in improving the odds of fertilization, both during natural conception and IV treatment.

Researchers from the University of Cambridge now show that human sperm swims similar to a fish swarm with their head facing the current. This rheotaxis allows fish swarms to adapt to counter flows. Using microfluidic devices, in which liquid is forced to flow through tiny channels, the researchers show that human sperm cells not just align against the counter flow, but move along the walls of the channels. The sperm cells end up spiralling along the edges of the oviduct. This increases the chance of meeting a potential egg and could so help the sperm cells find the egg. The researchers suggest that this could help in the design of artificial insemination, by for example optimizing the fluid used for fertilisation. Whether we can replace the beetle pose with something a tad more dignified is not known – yet.
Original paper in eLife: Rheotaxis facilitates upstream navigation of mammalian sperm cells – http://elifesciences.org/content/3/e02403