The unique connections of the brain in adolescence
A new study, conducted on mice, shows that in adolescence, not only are unnecessary connections between nerve cells removed, but new communication centers are created — the absence of which may be related to the development of diseases like schizophrenia.
Those who live in a house with teenagers are surely familiar with the eye-rolling, mood swings, endless conversations with friends behind a closed door, and generally a feeling of "you don't understand us." The physical changes they go through are easy to see — they grow taller, their bodies and voices change. But the changes occurring in the brain cannot be seen from the outside.
The article was originally published on the Davidson Institute of Science Education website. For years, the accepted approach to understanding the changes that happen in the brain during adolescence was that they stem primarily from a self-organization process called synaptic pruning. According to this approach, during childhood, a great many connections (synapses) are created in the brain between nerve cells. In adolescence, the brain clears out weak or useless connections to become more efficient and operate faster.
A new study, conducted on mice, showed that this process does indeed exist, but alongside it, areas also form along the nerve cell extensions that are characterized by an especially high density of synapses. The novelty of the current study is that this time the researchers did not settle for a general average of the number of synapses, but examined where they are distributed along the nerve cell extensions.
To prepare the mice brains for microscopic examination, the researchers used methods that allow for distinguishing details in the tissue at an exceptionally high level of detail of only hundreds of nanometers. The brains of mice of various ages were examined: one-week-old, two-week-old, and three-week-old pups, as well as adult mice aged 8-12 weeks. This division allowed the researchers to track the changes occurring in the mice's brains from two weeks of age until adulthood, a period that more or less corresponds to human adolescence. The researchers focused on an area in the brain that processes sensory input, and within it, on a layer of cells that receives information from the mouse's whiskers.
Advanced microscopic methods allowed them to examine all parts of the nerve cell: the cell body and the many extensions branching from it called the "dendritic tree." They tracked the dendrite — a kind of branch that emerges from the nerve cell body and branches out further. The high resolution allowed them to identify dendritic spines along it — a kind of protrusion on which there are synapses used for the passage of signals and information between nerve cells. The researchers also identified that the dendritic spines are not distributed uniformly along the extensions. In certain areas, an especially high density of dendritic spines with synapses was seen, and the researchers called these areas "hotspots."
In the brains of very young mice, no such sites were found, only in the brains of mice from adolescence onwards. When the mice's whiskers were trimmed, from which the input to this area of the brain arrives, there were fewer hotspots along the dendrite. In other words, the findings teach that sensory input is essential for the proper development of neural connections in this area.
However, the most intriguing discovery in the study relates to psychiatric diseases: post-mortem autopsies conducted in the past on the brains of people with schizophrenia found that their dendritic spine density is lower than normal. Therefore, the researchers sought to examine this in genetically modified mice that simulate schizophrenia patients. It was found that in young pups there was no difference in the amount of synapses between the modified mice and healthy mice. In contrast, in adolescence, a significant increase in the number of dendritic spines and the amount of synapses at the hotspots was documented in healthy mice, while in the modified mice, no such sites developed at all.
This finding shows that it is possible that the reduction in dendritic spine density in the brain of schizophrenia patients is not related to excessive synaptic pruning, but to a failure in the formation of synapses at the hotspots during the critical time window in adolescence. The study's findings raise fascinating research directions, but it must be remembered that the study was performed only on mice. Although mice are mammals, like humans, and there is a certain similarity in the structure of their cerebral cortex and ours, further studies are required to examine if a similar process indeed occurs in humans as well. In addition, the researchers focused on a specific type of nerve cell in the cerebral cortex, and it is possible that in other types of cells and other areas of the brain that were not examined in the study, other developmental processes occur.
