The nerve cells make life and death decisions depending on the location of the nerve damage. How do they determine the place of injury?
Later it will be forgotten as we are not
But when the evening lurks
I tell you so between us
Less but still painful
For what was wounded in me, wounded and iced
I hardly think
Learn to live with it that way
Less but still painful.
"Less but painful"
Words: Jonathan Gefen
Composed and performed by: Yehuda Polikar
A blow to the toe, a scratch on the knee, a burn on the tongue - no matter where the injury is caused, the result is the same: pain. But for the nerve cells, the position where they "absorb" the injury may be fatal. The distance between the site where the injury occurred and the nerve cell body - the "control center" of the cell that receives the information about the injury and decides on an appropriate response - is one of the factors that determine whether the damaged nerve cells will recover or die. In other words, the nerve cell's control center measures the distance between it and the injury site - but until now it was not clear how it does this.
Prof. Michael (Mike) Feinzilber and the post-doctoral researcher Dr. Naaman Kem from the Department of Biological Chemistry, and Prof. Yitzhak (Tzachi) Flapel from the Department of Molecular Genetics at the Weizmann Institute of Science, use computer methods and mathematical models with the aim of discovering the mechanism that enables the measurement of distances.
Dr. Kam: "Until today, any attempt to describe the mechanism was a 'shot in the dark', because we do not have enough data. In the current study, we examined several possible mechanisms with the aim of understanding which one is the one that has a higher probability that nature chose it, and uses it. This is how we prepare an infrastructure for more focused experimental research."
In the first step, the scientists examined a number of possible mechanisms, based on known data on the means of communication within nerve cells. These cells can create extensions that reach up to one meter in length (for comparison, the length of other cells does not exceed a few tens of microns). Therefore, in order for such a nerve cell to be able to transmit information from one end to the other, it must use methods that allow transmission of communication signals over great distances. They do this through a combination of electrical signals and chemical mediators which are transmitted through unique proteins, which serve as an "engine" that moves the signal molecules at a known speed. The scientists believe that the "control center" of the nerve cell uses these means of transportation for another purpose: to calculate the distance between it and the place of the nerve injury.
One mechanism that is examined is based on the duplication in the transmission of neural information: when an injury is caused, an electrical signal and a chemical signal are created at the same time, and both move to the center of the nerve cell to report this to the "control center". But the speed of the two signals is very different - roughly like the difference between the speed of a rifle bullet and that of a slow truck. This difference in the speed of two signals moving in the same path, allows to calculate the length of the path along which the signals passed. Another mechanism is based on the chemical signal only. Since the particles of the chemical substance - which transmit the signal - tend to disperse as they progress, they create a sort of cloud of particles that becomes thinner as the distance traveled by the signal increases. In order for nature to choose this mechanism, the cell body must be sensitive enough to detect the density differences between the particles, to notice the arrival of "waves" of chemical particles that have traveled different distances, and accordingly to calculate the distance required for such dispersion of particles.
What mechanism did nature choose? To try to answer this question, the scientists created a computational model and entered into it the data concerning the site of the nerve damage and the exact speed at which each signal moves. The resulting computer simulation showed that the "double signal" model - that is, the model that combines the arrival times of the electrical and chemical signals - indeed provides a fairly accurate basis for measuring distance in cases of nerve damage. On the other hand, the model based on the dispersion data of the chemical signal alone did not allow the "control center" to correctly calculate the distance of the nerve damage - so it seems that the nerve cells do not use this method. Thus the scientists concluded that both the fast electrical signals and the slow chemical signals are necessary for measuring long distances, and that it is likely that nature chose the double measuring mechanism. In addition, the double model provides quantitative and qualitative data at the same time.
By simulating two nerve injuries that occur at the same time, one at a site closer to the nerve cell body and the other further away, using the double measurement mechanism, the scientists were able to show that the nerve cell body is able to distinguish between two different injuries as long as the distance between them exceeds a tenth of the total length of the cell It was also discovered that there is a correlation between the reaction time and the distance. These results correspond to different species of animals whose nerve cells are of different lengths.
The findings were recently published in the scientific journal PLoS Computational Biology. Although it is a simple simulation of complex biological processes, this model is a springboard towards experimental research that can contribute detailed data on the methods that allow nerve cells to identify sites of nerve damage, and calculate the distance between the control center of the cell and the area of damage. The scientists hope that these new insights can lead, in the future, to the development of various medical applications. Among other things, it may be possible to disrupt the distance calculations performed by nerve cells to prevent cell death and encourage restoration processes.
