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Researchers at Leipzig University’s Carl Ludwig Institute have discovered that in the cerebral cortex, synaptic signal transmission between brain cells functions very reliably even at low concentrations of calcium ions – unlike in the rear region of the brain. The findings contribute to our understanding of the healthy brain, but may also prove useful to the computer industry, for example in the development of neural networks. The results were recently published in the prestigious journal Science.
Thinking, learning, feeling – all sensory perceptions are processed in the brain. Roughly 100 billion nerve cells are interconnected in the human brain. The lightning-fast communication between these brain cells, known as neurons, takes place primarily through signal transmission at their contact points, the synapses. This involves a complex interplay of electrochemical processes that bridge the tiny gaps between a sending cell and a receiving cell. The underlying mechanism is well known: put simply, synaptic signal transmission is triggered when calcium ions in the sender neuron bind to specific sensor proteins, which causes messengers – known as neurotransmitters – to be released from the cell. The receiving cell responds with a measurable electrical signal.
Differences in signal transmission
Nevertheless, there are significant differences between regions of the brain that can affect signal transmission, such as the size of the nerve cells, the number of synapses, and the properties of the calcium-binding sensor proteins within the cells.
“We have known for some time that transmission in the cerebral cortex is much more reliable than in other regions of the brain,” says Professor Hartmut Schmidt of the Carl Ludwig Institute (CLI) at the Faculty of Medicine, who led the study. The cortex is also known as the grey matter of the brain, which contains processing centres for various functions, such as the somatosensory cortex. This is the area where sensory impressions from the body are pre-processed before being passed on to other parts of the cortex.
Sensor protein plays a key role
“In our current study, we discovered that the sensor protein there – known as synaptotagmin 1 – already responds to much lower calcium concentrations in the synapse and triggers signal transmission. This is in contrast to the sensor protein synaptotagmin 2, for example, which is found in cells in the rear part of the brain and has been studied for 25 years,” explains the biologist. “The properties of synaptotagmin 1 appear to contribute to the fact that the cortical synapses we examined are not only more reliable, but also more plastic – a fundamental prerequisite for the brain’s ability to adapt to new demands over the course of life.”
Detailed knowledge of these factors in the healthy brain provides a foundation for identifying disrupted processes in brain disorders and for developing potential therapies. “But these findings could also be relevant to the further development of neural networks in the computer industry,” says Schmidt.
The researchers studied cells in the primary somatosensory cortex using brain tissue from mice. They combined several methods in their experimental series: using the patch-clamp technique, they measured the electrical signals of connected pairs of nerve cells. At the same time, they monitored and measured the calcium concentration in the synapses – using a UV laser and a two-photon laser microscope.
They also developed their own method, which they call “axon walking”. This makes it possible to locate the four to five synapses currently active along the nerve cell extensions, known as axons. These synapses are only about a thousandth of a millimetre in size.
Based on the data, the researchers developed a detailed mathematical model for the sensor protein under investigation. The model can also be used by other research groups. Current follow-up projects are examining whether synaptic transmission can be further differentiated across different regions of the cerebral cortex.
The study was funded by the German Research Foundation (DFG) and the European Research Council (ERC).
Author: Birgit Pfeiffer
Translation: Matthew Rockey
Professor Hartmut Schmidt
Leipzig University, Faculty of Medicine
Carl Ludwig Institute for Physiology
Phone: +49341 - 979715504
Email: Hartmut.Schmidt@medizin.uni-leipzig.de
https://doi.org/10.1126/science.adp0870 Original publication in Science: "The intracellular Ca2+ sensitivity of transmitter release in glutamatergic neocortical boutons"
Professor Hartmut Schmidt.
Quelle: Photo: Birgit Pfeiffer
Copyright: Leipzig University
The microscopic image shows a nerve cell and a magnified view of the investigated synapses. Calcium ...
Quelle: Photo Professor Hartmut Schmidt
Copyright: Leipzig University
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