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Stress Neurons Mapped the Brain, Exposing Estrogen Link

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summary: Researchers have identified specific neuronal groups in the mouse brain that are involved in negative emotional states and chronic stress.

Neurons mapped using a variety of advanced techniques were found to have estrogen receptors. This finding may explain why women are more vulnerable to stress than men.

This breakthrough has potential implications for the treatment of depression and anxiety disorders.

Important facts:

  1. Advanced techniques such as patch-seq, neuropixels, and optogenetics were crucial to the research’s success and aided in neuronal mapping and behavioral control.
  2. The researchers were able to influence mouse behavior through optogenetics, highlighting the direct role of these neurons in inducing behavior.
  3. This research could lead to the development of new treatments for depression and anxiety disorders by targeting these specific neurons and understanding how negative signals in the brain are generated. .

sauce: Karolinska Institute

Researchers at the Karolinska Institutet in Sweden have identified a group of neurons in the mouse brain that are involved in generating negative emotional states and chronic stress.

The neurons mapped using a combination of advanced techniques also have estrogen receptors, which may explain why women as a group are more sensitive to stress than men.

This research natural neuroscience.

This shows a neuron.
Science has long been unclear about which networks in the brain trigger negative emotions (disgust) and chronic stress.Credit: Neuroscience News

Science has long been unclear about which networks in the brain trigger negative emotions (disgust) and chronic stress.

Using a combination of advanced techniques such as patch-seq, large-scale electrophysiology (neuropixels), and optogenetics (see factbox), KI researchers Constantinos Meletis and Marie Karen and their team were able to map specific neuronal pathways in the body. The mouse brain running from the hypothalamus to the habenula nucleus that controls aversion.

The researchers used optogenetics to activate pathways when mice entered a particular room, and found that mice immediately began avoiding the room, even if there was nothing inside. bottom.

Paving the way for new treatments for depression

“We discovered this connection between the hypothalamus and the habenula nuclei in previous studies, but we didn’t know what types of neurons the pathway consisted of,” said the Karolinska Institutet Neuroscience Department. Professor Konstantinos Meletis says:

“It would be very interesting to understand which types of neurons in the pathway control disgust. We can also discover the mechanisms behind these affective disorders, paving the way for new drug treatments.”

The study was led by three postdoctoral fellows in the department: Daniela Calbigioni, Janos Fuzik and Pierre Le Maire. This is an example of how such techniques can be used to identify the neural pathways and neurons that control emotions and behavior.

sensitive to estrogen levels

Another interesting finding is that neurons associated with disgust have estrogen receptors, making them sensitive to estrogen levels. When male and female mice were exposed to the same type of unpredictable mild aversion event, female mice developed much more persistent stress responses than males.

“It’s been known for a long time that anxiety and depression are more common in women than in men, but we didn’t know the biological mechanisms that could explain it,” says neuroscience professor Marie Karen.

“We have now discovered a mechanism that can at least explain these sex differences in mice.”

This research was primarily funded by the Knut & Alice Wallenberg Foundation, the Swedish Research Council, the Swedish Brain Foundation, and the David & Astrid Hagelen Foundation. The researchers report no potential conflict of interest.

Factbox: Here are the techniques used

Patch sequence: Patch-seq combines the measurement of electrical properties of individual cells with the measurement of gene expression (RNA-sequencing) to allow mapping of different types of neurons in the brain.

Neuropixel: Neuropixels probes are a new type of electrode for large-scale electrophysiological measurements, capable of recording the activity of hundreds of individual neurons simultaneously.

Optogenetics: Optogenetics is used to control when and how selected neurons are active. This method involves introducing light-sensitive proteins (such as channel proteins from the membrane of unicellular organisms) into the studied neurons. Light can then be used to control individual cell types in the mouse brain to see how they function.

About this stress and neuroscience research news

author: Constantine Meletis
sauce: Karolinska Institute
contact: Konstantinos Meletis – Karolinska Institutet
image: Image credited to Neuroscience News

Original research: open access.
Esr1+ hypothalamic habenula neurons form an aversive stateby Constantine Meletis et al. natural neuroscience


Esr1+ hypothalamic habenula neurons form an aversive state

Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula nucleus (LHb) provoke an aversive response. We used patch sequence (Patch-seq)-based multimodal classification to define the structural and functional heterogeneity of the LHA–LHb pathway.

Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles and projection patterns.

We found that genetically defined LHA-LHb neurons signal different aspects of emotional or naturalistic behavior, such as estrogen receptor 1 expression (Esr1).+) LHA-LHb neurons induce aversion but express neuropeptide Y (Npy+) LHA-LHb neurons control rearing behavior.

Optogenetic-driven repeats of Esr1+ LHA-LHb neurons behaviorally induced a sustained state of aversion, and large-scale recordings showed a region-specific neural representation of aversive signals in the anterior limbic region of the prefrontal cortex.

Moreover, in female mice, exposure to unpredictable mild shocks induces sex-specific susceptibility to develop a stress state, which is associated with specific changes in burst Esr1-specific properties. I also discovered that there is+ LHA-LHb neurons.

In summary, we describe the diversity of LHA-LHb neuron types and provide evidence for a role for Esr1.+ Neurons of disgust and sexual dimorphic stress sensitivity.

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