Optical approaches to identify ion channels and their function

Our thoughts and actions are generated by a network of billions of nerve cells that communicate through electrical and chemical signals. Neurons are anatomically complex cells and have distinct regions for receiving and sending signals. When the received information surpasses a certain threshold, an electrical signal is initiated and distributed to other cells.

To generate electrical impulses, nerve cells maintain gradients of charge across their membrane by pumping ions in and out of the cell. Classic electrophysical work has established how the precisely timed opening of sodium and potassium channels generates an electrical pulse. These pulses originate in a special region of the cell: the axon initial segment (AIS).

While we know a lot about ion fluxes in the AIS, there are still processes and channels in the AIS that we have not identified. The AIS is a thin structure which makes it hard to record with electrophysiological means. However, electrical signals can be recorded optically using fluorescent molecules, enabling live measurement of ionic signaling while a cell is active. Furthermore, recent advances in microscopy revealed that ion channels at the AIS follow a nanoscale periodic structure.

In this thesis we asked the questions how ion signaling and the periodic organization at the AIS shape the generation of electrical signals. In order to answer these questions, we need to bridge functional investigations with high resolution structural reconstructions.

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