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April 24th 2019

Information transfer between nerve cells in the brain is made possible by receptor proteins in synapses, the contact points between cells where signals are passed on in the form of molecules. How brain cells are connected with each other determines the pathways in neural networks (the brain). We now know that these pathways are not only dependent on whether cells are connected or not but also on the strength of the connection between cells. It seems that the regulation of this strength plays a crucial role processes associated with learning and memory. 

Regulating receptors
How strongly brain cells are connected with each other is largely determined by the quantity of receptors on the receiving side of the synapse awaiting the signal. The processes that enable the nerve cell to change receptor concentrations are, however, poorly understood.

The aim of this FOM programme is to decipher these processes. The researchers are examining mainly how receptors are transported into the synapses and then kept there. FOM PhD researcher Remy Kusters (Eindhoven University of Technology) together with programme members in Utrecht realised a first breakthrough that was published in Biophysical Journal in 2013. His work has provided insights into the role played by synapse shape in the transport processes.

Fighting against diffusion
Retaining the receptors is a challenge for the synapses. That is because receptors are attached to the cell membrane, which is effectively a fluid environment. The receptors therefore have the tendency to flow away just like a spot of ink that inevitably spreads out. However, to achieve a constant strong connection between nerve cells, the receptor concentrations must remain high for a long time. The cell realises that with the help of strongly curved structures in the membrane, the so-called dendritic spines: dynamic structures with a variety of shapes. Using simulations and analytical calculations, Kusters has demonstrated that these structures have a major effect on the diffusion rate of the receptors. The membrane shape is therefore a very suitable means of regulating receptor concentrations.