"See here," says molecular neurobiologist Casper Hoogenraad as he draws neurons (nerve cells) on a blank sheet of paper. "During its development, every neuron makes two types of extensions: a number of dendrites and a single axon. Dendrites receive information which forms the input for the cell, and the axon transmits information from the brain to the rest of the body. We will soon be able to observe and study for the first time the way in which the 'skeleton' of the neuron develops and how it contributes to the organisation of the brain." The whole world is watching. Knowledge of the construction of the 'neuron skeleton' and the transport of information along it can give us insight into disruptions that occur in brain diseases such as Alzheimer's and ALS. What is more, the professor and his researchers will also be able to manipulate the development and growth of neurons.
"We are now reaping the benefits of the initiative by Utrecht University and the Faculty of Science a few years ago to invest in fundamental research in cell biology and a top-class imaging facility." This is also what brought Hoogenraad to Utrecht. "In this ERC project, we are using advanced microscopes to study the development of the skeleton within a neuron in three stages: the construction and organisation of the skeleton and the transport along the skeleton. The question is: how does the polarity of the neurons come about, with the dendrites on the one side of the cell and the axon on the other. The axon and the dendrites each require different materials. How does a neuron know where to bring the different building blocks?" It is an extensive system: the human brain contains over 100 billion neurons. The system is also vulnerable. Once damaged, neurons are hard to repair.
Cultured brain cells
The researchers study brain cells outside the brain, a prime example of the excellent research carried out in Utrecht. Hoogenraad explains with pride: "We are working together with the Hubrecht Institute and University Medical Center Utrecht. For some years now, we have been able to keep neurons alive outside the body." Their research is renowned worldwide. "I have just come back from an international meeting, where researchers from all over the world are following our research with great interest. We are the only people using light-sensitive systems to allow neurons to grow. So it's great to be able to invite them to observe."
Hoogenraad takes great care in putting his research team together: "I gather young scientists who have a passion for microscopy and who study the growth and development of the neuron very carefully and meticulously. It is also important to me that researchers communicate with each other. You can only take major steps forward if you are willing to share knowledge and are open to discuss your work."
"Studying neurons as they develop can teach us a great deal about the brain, a subject about which we know far too little. Ultimately, the question is how neurons in the brain make connections and together form the 'human memory'. It really is extraordinary that neurons are capable of storing information. No other cell in our body can do this. We now know roughly where this takes place – in the synapses, the points of contact between the neurons – but we still don't know how. And how is it that neurons in different parts of the brain have different functions? One cell 'smells', while another 'sees', yet they all start out as identical cells with the same genetic content."
The researchers are not just observers. "We are able to manipulate cell biological processes. If we remove certain molecules for example, or administer drugs, we can observe how this affects the way neurons develop and function. Interventions such as these could enable us to repair disruptions in neurons."
It's just a matter of time until the breakthrough.
Written by: Youetta Visser