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What is happening at synapses?

How are thoughts generated? And how do we remember things? Professor Peter Jonas from the Institute of Physiology I at the University of Freiburg believes a network of nerve cells in our brain is responsible for all this. As the proper function of the network depends on the kind of contacts between the individual neurons, Jonas is investigating processes that occur at these contact sites, i.e. the synapses. He is cooperating closely with other colleagues from Freiburg and from Basel (Switzerland) with whom he has established a joint special research area (SFB 780) on the topic "Synaptic mechanisms of neural network function".

Every day, the human brain is exposed to a flood of environmental stimuli. How does it filter relevant information from this chaos? How does it encode this information? How does it store this information and recall it at a later time? These processes are generated through complex neural networks in the brain. The human brain consists of approximately 1011 neurons. The individual cells of the brain need to interact in a network so that they are able to perform incredible actions such as thinking or memory. As the properties of such a network are determined by the contact sites between the nerve cells, these contacts, or synapses as these contacts are called, play an important role in generating mental activity.

Beyond text book knowledge

Synapses seen under the electron microscope. (Photo: Prof. Michael Frotscher and working group Prof. Peter Jonas)
Nerve cells transmit information to other nerve cells across synapses. The axons (long, slender projections of nerve cells) conduct this information as electrical impulses away from the nerve cell body. At the presynaptic nerve terminal, membrane vesicles containing neurotransmitters are released into the synaptic cleft between the cell that transmits information and its communication partner on the other side of the synapse. The neurotransmitters then trigger certain ion channels on the membrane of the nerve cell on the other side of the synapse where they generate an analogous electrical signal. At least that is the current theory.

“Present knowledge about what happens at synapses comes from experiments involving a few nerve cell types,” said Peter Jonas, Director of the Institute of Physiology I at the University of Freiburg and coordinator of the SFB 780. “Current knowledge gives us a general idea of what is going on and it is not possible to generalise about all nerve cell types.” Do all synapses function in the same way or do synapses of the higher brain centres differ from other synapses to a far greater degree than previously assumed? Far too little is known about what happens in the nerve cells in regions such as the hippocampus, which plays an important role in storing information and hence is important for memory and thinking.

The fundamentals of thinking and memory

Hippocampus with some nerve cells and their projections. (Figure: Cajal, 1911)
The 17 research groups from Freiburg and Basel are working together in the SFB 780, using different tools to elucidate the function of synapses in the brain from different perspectives. For example, some researchers are simulating neural networks on the computer. Others are using modern imaging methods to visualise the exact structure of synapses. The team of researchers led by Peter Jonas is investigating synapses in the hippocampus of rats and mice. The researchers are interested in what happens on the presynaptic side of a neural junction, i.e. where the membrane vesicles containing the neurotransmitters are released.

Using new methods, Jonas and his team succeeded, for the first time ever, in determining the electrophysiological processes at the presynaptic side of a specific type of hippocampal synapse (mossy fibre synapse). The researchers found that this type of synapse had many similarities with other, previously investigated synapses. However, they also found some differences which can most likely be accounted for by the special function of the hippocampal network.

The electrical properties of mossy fibre synapses are not stereotypic but change upon repeated stimulation. In addition, they have a far bigger pool of neutrotransmitter vesicles than other synapses. “These findings suggest that the mossy fibre synapses underlie a very distinct dynamic,” said Jonas adding that this “is most likely related to plasticity processes that are typical for hippocampal cells and that might be the basis of memory.”

Mental processes and pathological disorders

An interneuron (right) and two of its communication partners in the hippocampus (Photo: Working group Prof. Peter Jonas)
Another project which Professor Jonas and his team focus on involves hippocampal interneurons. They are called interneurons because they remain in one cell layer and do not extend their projections into other cell layers. In contrast to other hippocampal cells, they release an inhibitory neurotransmitter substance. That is why they have an inhibitory effect on other cells. They represent an important counterweight in the neural network. Jonas and his team discovered that a subpopulation of the interneurons is able to process information extremely quickly. This characteristic might make possible mental activity which requires a highly temporal synchronisation of activity between entire neural networks, such as for example visual perception.

Within a period of 12 years and within the SFB 780, Jonas and his fellow researchers are hoping to elucidate how the brain works. They are not only hoping to gain deeper insights into how thinking and memory works; they are also hoping that their findings will benefit patients who suffer from diseases such as epilepsy or depression. It is known that defective synaptic transmission plays a central role in many pathological disorders.

mn – 30th April 2008
© BIOPRO Baden-Württemberg GmbH
Further information:
Prof. Dr. Peter Jonas
Institute of Physiology, Department I
Hermann-Herder-Str. 7
79104 Freiburg
Tel.: +49 (0)761/203-5151
Fax: +49 (0)761/2035204
E-mail: Peter.Jonas@physiologie.uni-freiburg.de
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/what-is-happening-at-synapses