
Researchers at the Carl Ludwig Institute at Leipzig University have discovered that synaptic signal transmission between brain cells within the cerebral cortex functions very reliably even with small amounts of calcium ions, unlike in the posterior region of the brain. The findings are a further building block for understanding the healthy brain, but could also prove useful for the computer industry when it comes to developing neuronal networks, for example. The results were recently published in the journal Science.
Thinking, learning, feeling - sensory perceptions are all processed in the brain. In humans, around 100 billion nerve cells are networked there. The lightning-fast communication between these brain cells, also known as neurons, takes place primarily as signal transmission at the contact points, the synapses. This is a complex interplay of electro-chemical processes in which the tiny gaps between a transmitting cell and the receiving cell are bridged. The underlying mechanism is well known: In very simplified terms, synaptic signal transmission is triggered when calcium ions located in the transmitter nerve cell bind to specific sensor proteins and, as a result, messenger substances, so-called neurotransmitters, are released from the cell. The recipient cell reacts with a measurable electrical signal.
Differences in signal transmission
Nevertheless, there are significant differences in various areas of the brain that can affect signal transmission: for example, the size of the nerve cells, the number of synapses and also the nature 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 Hartmut Schmidt from the Carl Ludwig Institute (CLI) of the Faculty of Medicine, head of the present study. The cortex is also known as the gray matter of the brain, which contains processing centers for various functions, such as the somatosensory cortex. This is the area in which sensory impressions are pre-processed by the body before being passed on to other areas of the cortex.
Sensory protein is crucial
"In our current work, we have discovered that the sensor protein there, called synaptotagmin 1, already reacts to a much lower calcium concentration in the synapse and triggers signal transmission than, for example, the sensor protein in cells in the posterior region of the brain, synaptotagmin 2, which has already been researched for 25 years," says the biologist. "The properties of synaptotagmin 1 appear to contribute to the fact that the cortical synapses we investigated are not only more reliable, but also more plastic - a basic prerequisite for the brain to be able to adapt to new requirements throughout life."
Precise knowledge of these factors in the healthy brain provides the basis for recognizing disturbed processes, for example in brain diseases, and developing therapeutic approaches. "But these findings could also be relevant for the further development of neuronal networks in the computer industry," says Schmidt.
Detecting active synpases
The cells in the primary somatosensory cortex in the brain tissue of mice were investigated. For their series of experiments, the researchers combined several methods: they measured the electrical signals of connected pairs of nerve cells using the patch-clamp technique. At the same time, they controlled 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 track down the four to five active synapses along the nerve cell processes known as axons. These are only around one thousandth of a millimeter in size.
Using the data, the scientists developed a detailed mathematical model for the investigated sensor protein, which can also be used by other research groups. Current follow-up projects are dedicated to the question of whether synaptic signal transmission can be further differentiated within different areas of the cerebral cortex.
The study was funded by the German Research Foundation (DFG) and the European Research Council (ERC).
Original publication in Science:
"The intracellular Ca 2+ sensitivity of transmitter release in glutamatergic neocortical boutons", https://doi.org/10.1126/science.adp0870