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Section A

Cellular level

On the cellular level, in research section A, we will ask: How do supramolecular complexes and interacting subcellular structures contribute to adaptive single neuron computation? Projects in section A are aiming to achieve new levels of quantitative precision and integration for studies of single neuron computation. In single neuron modelling it is widely appreciated that neurons are spatially extended complex systems and many lines of evidence indicate that the spatial heterogeneity of ion channel properties in their compartments is functionally very important. There is, however, currently no truly quantitative approach to map the heterogeneity of ion channel properties in individual neurons. Projects A2 (Enderlein/Neef) and A4 (Schmidt/Neef) will pioneer two complementary methods to achieve this important goal and may well revolutionize data driven model building on the single neuron level. Their complementary approaches are based on biophysical methods developed to achieve single molecule resolution in fluorescence imaging (PALM, STORM) and ion channels localization (SICM) and will use them to quantify the spatially inhomogeneous distribution of channels and ionic currents in cultured neurons. The closely linked project A3 (Stühmer/Wolf) will develop a new optogenetic approach to quantitatively characterize the dynamical properties of action potential generation and encoding in cultured cortical neurons. It will use neurons expressing light sensitive ion channels cultured on multi electrode arrays to emulate synaptic bombardment - the working condition of cortical neurons in vivo - in intact neurons not dialyzed by whole cell recording. This approach will be used to constrain models of action potential initiation and encoding in the soma-proximal axon complex of cortical cells and to dissect the contributions of different molecular components of this machinery. This set of three closely related projects is complemented by projects A1 (Göpfert/Schmidt) and A5 (Meyer/Moser/Wolf) that will perform case studies on paradigmatic sensory cells, mechanoreceptor neurons of the drosophila chordotonal organ and inner ear hair cells. These cells are serving a similar function, the transformation of sound into neural electrical activity in evolutionary widely separated species. Both projects, A1 and A5, are based on prior theoretical work that integrates previously accumulated data and enables to pose questions at a highly quantitative level. Achieving a comprehensive and quantitative link between sensory function and subcellular/molecular organization in these systems has recently come within reach by steady progress in the genetic manipulation of mouse and drosophila hearing. In these systems, combining optical approaches for mechanical stimulation and subcellular functional imaging with quantitative analysis and modelling of subcellular processes will reveal a previously invisible layer of cooperative dynamics in the cellular basis of hearing.

Projects involved: