Researchers find neurons linked to chronic stress

A set of nerve cells in the mouse brain have been shown to play a role in the development of unpleasant emotional states and long-term stress, according to researchers at Sweden's Karolinska Institutet. The neurons, which have been mapped using a variety of cutting-edge methods, also include oestrogen receptors, which may help to explain why women are generally more sensitive to stress than males.

The findings of the study were published in Nature Neuroscience.

Science has long been unsure about precisely which brain networks give rise to unfavourable emotions (aversion) and persistent stress.

KI researchers Konstantinos Meletis and Marie Carlen and their group have been able to map out a particular neuronal pathway in the mouse brain connecting the hypothalamus to the habenula that regulates aversion by combining cutting-edge techniques like Patch-seq, large-scale electrophysiology (Neuropixels), and optogenetics (see fact box).

The mice quickly began to avoid the room, even though there was nothing inside after the researchers used optogenetics to activate the circuit when the mice entered a specific room.

"We discovered this connection between the hypothalamus and the habenula in a previous study but didn't know what types of neurons the pathway was made up of," says Konstantinos Meletis, professor at the Department of Neuroscience, Karolinska Institutet. "It's incredibly exciting to now understand what type of neuron in the pathway controls aversion. If we can understand how negative signals in the brain are created, we can also find mechanisms behind affective diseases like depression, which will open the way for novel drug treatments."

The study was led by three postdocs at the same department, Daniela Calvigioni, Janos Fuzik and Pierre Le Merre, and as Professor Meletis explains, is an example of how scientists can use advanced techniques to identify neuronal pathways and neurons that control emotions and behaviour.

Sensitive to estrogen levels

Another interesting discovery is that the neurons linked to aversion have a receptor for oestrogen, making them sensitive to oestrogen levels. When male and female mice were subjected to the same type of unpredictable mild aversive events, the female mouse developed a much more lasting stress response than the male.

"It has long been known that anxiety and depression are more common in women than in men, but there hasn't been any biological mechanism to explain it," says Marie Carlen, professor at the Department of Neuroscience. "We've now found a mechanism that can at least explain these sex differences in mice.