Newswise — A team of scientists from the Karolinska Institutet in Sweden has made a significant discovery regarding a cluster of nerve cells within the mouse brain. These cells play a crucial role in generating negative emotional states and chronic stress. By utilizing a combination of cutting-edge techniques, the researchers successfully mapped out these neurons. Intriguingly, they found that the cells possess receptors for estrogen, providing a potential explanation for the greater susceptibility of women to stress compared to men. The findings of this study have been published in the prestigious journal Nature Neuroscience.
Just which networks in the brain give rise to negative emotions (aversion) and chronic stress have long been unknown to science.
Utilizing a comprehensive array of advanced techniques including Patch-seq, large-scale electrophysiology (Neuropixels), and optogenetics, a group of researchers from the Karolinska Institutet (KI) comprising Konstantinos Meletis, Marie Carlén, and their team have successfully charted a distinct neural circuit within the mouse brain. This pathway, extending from the hypothalamus to the habenula, exerts control over aversive responses. The combination of these cutting-edge methodologies has provided unprecedented insights into the intricate workings of this specific neuronal connection.
In their investigation, the research team employed optogenetics to stimulate the identified pathway when the mice entered a specific room. Fascinatingly, the mice exhibited a noteworthy behavioral response: they began to avoid the room, despite the absence of any discernible stimuli within it. This outcome highlights the influential role of the activated pathway in generating aversive behaviors and underscores the profound impact of neuronal activity on the mice's subsequent behavior.
Opens the way for novel treatments for depression
According to Konstantinos Meletis, a professor at the Department of Neuroscience, Karolinska Institutet, the team had previously identified the connection between the hypothalamus and the habenula, but they were uncertain about the specific types of neurons that constituted this pathway. Meletis expresses his enthusiasm regarding the recent breakthrough, stating that it is exceptionally exciting to now comprehend the neuron type within the pathway that governs aversive responses. Understanding the underlying mechanisms of negative neural signaling holds immense potential in unraveling the complexities of affective disorders such as depression. By gaining insight into the creation of negative signals in the brain, novel avenues for developing drug treatments may be unveiled, offering promising prospects for addressing these conditions.
The study, spearheaded by three postdoctoral researchers Daniela Calvigioni, Janos Fuzik, and Pierre Le Merre, within the same department, exemplifies how scientists can leverage sophisticated techniques to identify specific neuronal pathways and individual neurons involved in regulating emotions and behavior. Professor Meletis emphasizes that this study serves as a prime demonstration of the power of employing advanced methodologies to unravel the intricate workings of the brain and uncover the fundamental mechanisms governing emotional and behavioral responses. The collaborative efforts of the postdocs and their team have significantly contributed to expanding our understanding of the neural underpinnings of emotions and behavior.
Sensitive to oestrogen levels
Another intriguing finding is that the neurons associated with dislike possess a receptor for oestrogen, rendering them responsive to oestrogen levels. Upon exposure to identical unpredictable mild adverse events, the female rodent exhibited a considerably more enduring stress reaction compared to the male.
"It has been widely acknowledged that the prevalence of anxiety and depression is higher among women compared to men, yet a concrete biological mechanism elucidating this disparity has been lacking," asserts Marie Carlén, a professor in the Department of Neuroscience. "However, we have now discovered a mechanism that can potentially account for these sex differences, at least in mice."
The study received primary funding from the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Swedish Brain Foundation, and the David and Astrid Hagelén Foundation. The researchers disclose no apparent conflicts of interest.
Factbox: Here are the techniques used
Patch-seq: Patch-seq merges evaluations of the electrical characteristics of individual cells with assessments of gene expression (RNA sequencing), enabling the mapping of distinct neuron types within the brain.
Neuropixels: The Neuropixels probe is an innovative electrode designed for conducting extensive electrophysiological recordings, enabling the simultaneous monitoring of activity in hundreds of individual neurons.
Optogenetics: Optogenetics is a technique employed to regulate the activity of specific neurons, determining when and how they become active. This method involves introducing light-sensitive proteins, such as channel proteins derived from the membranes of single-cell organisms, into the target neurons for study. By utilizing light, it becomes possible to manipulate individual cell types within the mouse brain and investigate their respective functions.
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