Journal of Physiology Consulting Editors - Bert sakmann

My current field of research is focused on the elucidation of neural circuits that drive a simple behaviour. An example of such a simple behaviour would be decision making based on a sensory input, let's say a tactile input, or a visual input. To put this in context it's estimated that about 1000 decisions are made per day per human. In order to elucidate neural circuits there are two areas of research, or areas of knowledge which you have to have to understand decision making on a mechanistic basis. One is you have to have a 3D reconstruction of the neural circuit that underlies decision making. And the second type of knowledge is you must know the pattern of electrical signals that is sweeping through this circuit before the decision is made and when the decision is made. You have a 3D coordinate system and within the 3D coordinate system you can register 100s or 1000s of neurons so that they will represent the anatomy of a part of the cortex, let's say of a whole cortical area. That's one part. The other part is that this network of cells then has to be made live by introducing electrical signals and watching the flow of signals through this network. And the aim is to be as exact and as close as possible to what is happening in the real tissue. What we have found out as a major finding is the simultaneous representation of a sensory stimulus in different cell types, specific cell types. And secondly we found out that the major determinant of the activation of these cortical cells, by the underlying activity in the thalamus, is the synchronicity of the electrical signals in the thalamus. The challenges in circuit analyses can be summarised by a new word that has been invented or created over the past few years and this is called 'Connectomics'. It means that to elucidate a neural circuit you have to have a detailed map, an anatomical map, of all the cells that are participating in a neuronal circuit, and there are various ways to do this. There is a light microscopic level but there is also now an electron microscopic level which will, in the future, enable us to have a complete 3D model of a pathway or, in the somewhat more distant future, of a whole cortical area or of the whole cortex. The task is to look at large ensembles of general behaviour at cellular resolution or even molecular resolution. The second challenge is to find out which of the mechanisms described under very simplified conditions are applicable in the intact organ. And the last challenge will be to find out which of these mechanisms that are present in human tissue is compromised in pathological conditions and there are many examples, for example Parkinson's disease, there are many many challenges.