Focus on Research: medical biologist Natalie Cappaert
A couple of weeks ago medical biologist Natalie Cappaert and her colleagues in the Cellular and Systems Neuroscience research group moved into a new building at Science Park Amsterdam. Though she does not have her full set of equipment yet, once the hassle of relocating is over, Cappaert hopes to quickly resume her research into communication in the brain.
Cappaert is interested in the hippocampus, a region of the brain that in rats is located above the ears and that, in both rats and humans, plays a role in learning and memory. The brain is flexible to a certain degree: with training, connections between nerve cells can change. This is what memory is, Cappaert explains. She cites the example of London cabbies. MRI studies have shown that their hippocampi are enlarged. ‘Which is purely because they spend all day searching for streets.'
In her research Cappaert is trying to understand the function of different parts of the brain and their interconnections by electrically stimulating certain connections and registering the activity. For example, Cappaert studies what happens when a specific region of the brain is stimulated by two different subareas: is the result of simultaneous stimulation by these subareas equal to the linear sum of its parts or is there an additional effect? She presented her findings in an article published in 2007. Stimulating different areas separately, it turned out, produced the same amount of activity as when the areas were stimulated simultaneously.
For her research, Cappaert uses a microtome to cut 400-micrometre thick sections of the hippocampus and the adjacent cortex. Slicing just right is difficult as all the connections have to remain functional. ‘But with knowledge of anatomy, it's possible to make an "educated guess". And then with some experience, you can obtain a properly functioning slice.'
A brain section can be kept alive for up to eight hours in the right medium, allowing researchers like Cappaert to study the brain under a microscope in vitro. If the slices are cut just right, she explains, the nerve cells can continue to communicate with each other.
Some areas activate each other, while others have an inhibiting effect, Cappaert says. Using small electrical currents, she stimulates groups of neurons and examines if and where reactions occur and within which time span. Reactions, in the form of small electrical voltage changes, are made visible with voltage sensitive dye imaging. This technique involves binding a special dye to the cell membranes, which absorb varying degrees of light depending on the voltage running over the membrane. ‘The advantage of this technique is that it allows you to examine a larger area and not just a couple of cells, as is the case with the more traditional electrophysiological methods.' The differences in absorption are analysed, resulting in images that display the amount of electrical activity in various hippocampal regions.
According to Cappaert, the hippocampus is perfect for this type of research. ‘It is a well-organised area of the brain. The neurons are neatly arranged and we know a lot about where specific neurons are located.' Scientists currently know of approximately 1600 connections between the various subareas of the hippocampus and the associated cortex.
‘No one can commit that many connections to memory', says Cappaert, ‘and I do find that frustrating'. During her research, she had to constantly refer to publications to check the various connections in the hippocampus. There are several review articles available, but those are based on the data of various animal species. Cappaert therefore decided with her then-colleagues Niels van Strien and Menno Witter to embark on a mammoth task: a complete survey of all known connections between regions of the hippocampus and associated cortex in the rat brain.
‘It started out as a hobby we were doing on the side', she says. ‘Niels and I would first have something to eat together after work and then spend a couple of hours in the evening working on this survey. But toward the end we were spending entire days on the project'. Five years of hard work certainly bore fruit, with an interactive and fully searchable diagram showing all connections. ‘It was published in Nature Reviews Neurosciences in April 2009 and of course we are very pleased about that', Cappaert says, adding that the article was also well received by colleagues. The website ‘Faculty of 1000 Biology' - which evaluates current research - classified it as exceptional and awarded an outstanding score of 9 points.
Cappaert is pleased with the attention all this has generated for anatomy, which, according to her, is a rather undervalued area in brain research. Far more research is devoted to the genetic and molecular aspects of the brain. And yet there is so much we do not know about the brain, Cappaert feels. ‘Actually, I find so many aspects of the brain interesting. The brain is where it all happens. I am currently trying to limit myself to studying the combined actions of neurons that activate and inhibit each other. The timing of these actions is also very important: for example, what would the effect be if I stimulated an inhibiting area a few milliseconds later than an activating area?'
Cappaert is enthusiastic about the idea of her own research group. ‘My group is currently composed of just me. I am trying to develop proposals for grants. With more people, I will also be able to expand the scope of my research.' And what about a professorship? ‘No, certainly not yet. Conducting my own research is far too much fun.'
Bachelor’s in Psychobiology
In addition to research, Natalie Cappaert spends much of her time teaching. She says she got into teaching after receiving a Veni grant from the Netherlands Organisation for Scientific Research (NWO) in 2004 and started tutoring first-year students. She is involved in renewing the curriculum of the Psychobiology Bachelor's programme. This programme previously consisted of subjects in biology and psychology, but there was little integration between them, Cappaert says. ‘It didn't work. Now teachers from both biology and psychology are involved in each subject offered in the Psychobiology study programme.' Cappaert herself teaches the Perception and Visual Consciousness course together with a couple of colleagues. Here she has students use their own observations to, for example, calculate the constant in Weber's law. This law states that people are better able to perceive small differences in stimuli when the intensity is low rather than high, since sensitivity is relative and not absolute. The course and the study programme are progressing well, Cappaert reports. ‘The Psychobiology programme has received a good accreditation and the students are enthusiastic.' Developing and delivering good-quality education is very time-consuming and that eats into the time available for her research, she says. ‘But it's certainly worth it and it's all part of working at a university.'