Our brain cells and negative emotions - some recent findings

What biological mechanisms govern negative emotions? Researchers in Sweden at the Karolinska Institute have found clues by studying mice's nerve cells that induce prolonged stress.

It has previously been unknown which networks in the brain give rise to negative emotions, so-called aversion, and prolonged stress states.

However, researchers at the Karolinska Institute have mapped a specific neural pathway in mice using various advanced techniques. This neural pathway runs from the hypothalamus to the habenula in the brain and controls negative emotional states.

The study used optogenetics - light-controlled activation of selected nerve cells - to activate the neural pathway when mice entered a specific room. The mice soon began to avoid the room, even though nothing existed.

"We discovered this connection between the hypothalamus and the habenula in previous work, but it was not known what types of nerve cells are in this neural pathway. It is inspiring to understand now what type of nerve cell in the pathway controls aversion," says researcher Konstantinos Meletis at the Karolinska Institute and continues:

"If we can understand how negative signals in the brain are created, we can also find the mechanisms behind affective disorders like depression. It opens up entirely new medication treatments."
Sensitive to estrogen levels

Another finding is that the nerve cells associated with negative emotions have a receptor for estrogen and are thereby sensitive to estrogen levels. When male and female mice were exposed to the same disturbance - mild electric shocks - the female mice developed prolonged stress states. The male mice were not affected to the same extent.

"It has long been known that anxiety and depression are more common in women than men, but no biological mechanism exists to explain it. Now we have found a mechanism that can explain these gender differences in mice," says researcher Marie Carlén at the Karolinska Institute.

The study is an example of how advanced techniques can be used to identify neural pathways and nerve cells that control various emotions and behaviors, according to the researchers who are explaining the following methods:

Patch-seq combines measurements of the electrical properties of individual nerve cells with measurements of gene expression (so-called RNA-sequencing) and makes it possible to map the brain's different nerve cell types.

Neuropixels are a new type of electrode for large-scale electrophysiological measurement that makes it possible to map the activity of several hundred individual nerve cells simultaneously.

Optogenetics is used to control how and when selected nerve cells are active. The method involves introducing light-sensitive proteins, for example, channel proteins in cell membranes from single-celled organisms, into the nerve cells to be studied. With the help of light, one can then control individual types of nerve cells in mice to find out their function.

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