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Mapping the brain's connections is no trivial task, there are estimated to be one hundred billion nerve cells ('neurons') in the brain, each connected to thousands of other nerve cells making an estimated 150 trillion synapses. Dr Tom Mrsic-Flogel, a Wellcome Trust Research Career Development Fellow at University College London (UCL), has been leading a team of researchers trying to make sense of this complexity.
"How do we figure out how the brain's neural circuitry works?" he asks. "We first need to understand the function of each neuron and find out to which other brain cells it connects. If we can find a way of mapping the connections between nerve cells of certain functions, we will then be in a position to begin developing a computer model to explain how the complex dynamics of neural networks generate thoughts, sensations and movements."
Nerve cells in specific areas of the brain perform different functions. Dr Mrsic-Flogel's group focuses on the visual cortex, which processes information from the eyes. For example, some neurons in the visual cortex detect only the edges of images; becomming active only upon detecting a horizontal edge, or a vertical edge.
Higher up in the visual hierarchy, some neurons respond to more complex visual features such as faces. Lesions to this area of the brain can prevent recognition of faces, even when the same individual can recognise individual features such as eyes and the nose. Dr. Oliver Sachs famously described such cases in his book "The Man Who Mistook Wife for a Hat."
The study is published online in the journal Nature, where a description of the technique (developed in mice) explains how they combined information about the function of neurons with details of each synaptic connection.
Using high resolution imaging of the mouse brain, the scientists were able to detect which neuron responded to a particular stimulus. The researchers then applied small currents to a subset of neurons to see which other neurons responded pinpointing which were synaptically connected. Through continual repeations of this technique, the researchers traced the function and connectivity of nerve cells in the mouse visual cortex.
The study has resolved a debate about whether local connections between neurons are random connecting sporadically, independent of function or whether they are ordered constrained by properties of a specific neuron responding to a specific stimuli. The researchers showed that neurons which responded very similarly to visual stimuli, tend to connect to each other.
The researchers intend to generate a wiring diagram first of the visual cortex, then apply the technique to reveal the wiring of regions covering touch, hearing and movement.
"We are beginning to untangle the complexity of the brain," says Dr Mrsic-Flogel. "Once we understand the function and connectivity of nerve cells spanning different layers of the brain, we can begin to develop a computer simulation of how this remarkable organ works. But it will take many years of concerted efforts amongst scientists and massive computer processing power before it can be realised."
The research was supported by the Wellcome Trust, the European Research Council, the European Molecular Biology Organisation, the Medical Research Council, the Overseas Research Students Award Scheme and UCL.