Nat Commun Xu Tianle/Li Weiguang/Zhang Siyu teamwork reveals the neural circuit organization law of "one-click switching" of good and bad emotions

Emotions and emotions are vivid and diverse, which is an indispensable part of a good life, and it is also an important guarantee for human beings and animals to seek benefits and avoid harm, survival and reproduction and social interaction [1
].

There are good and bad emotions, good emotions (also known as positive emotions) promote healthy human life and survival and development, and bad emotions (also known as negative emotions) are closely related to
a variety of major brain diseases.

The brain's neural mechanisms for the recognition, processing of good and bad emotions and their different emotional transitions [2] is one of the most fascinating research directions in the field of
brain science.

On September 21, 2022, the team of Professor Xu Tianle and Zhang Siyu of the School of Basic Medical Sciences of Shanghai Jiao Tong University, the National Children's Medical Center (Shanghai) Children's Brain Science Center, and Li Weiguang, a researcher at the Institute of Brain Science Transformation of Fudan University, published Insular cortical circuits as an executive gateway to decipher online in Nature Communications A research paper on threat or extinction memory via distinct subcortical pathways
.

With the help of cutting-edge techniques in neuroscience, this study found in the insular cortex of the brain that are responsible for characterizing negative emotions related to fear memory and positive emotional neuron clusters related to regression memory, respectively, in view of the neural mechanism of coordination and balanced expression of threatening fear memory and safe regression memory, and explained the neural circuit organization rules of two emotional memory neuron clusters at different levels such as "intercortical - intracortical - subcortic".
It provides an important theoretical basis
for understanding the interaction and dynamic transformation between negative emotions and positive emotions, and improving the understanding of the complex nature of emotional memory.

In this study, Xu Tianle's team focused on negative emotions related to fear memory and positive emotions related to regressing memory[3], focusing on the multimodal sensory integration center - island cortex [4], focusing on the analysis of two neuronal clusters of opposite emotional processing, and further expounding the organizational principles of constructing emotional memory neural circuits across brain regions [5].

1.

Using neural activity capture markers[6] combined with neural loop projection tracing, the researchers found that both fear memories and regressive memories were stored in the insular cortex (IC).
Clusters of fear memory neurons are preferentially projected to the central amygdala (CeA) brain region, while regressive memory neuron clusters are projected primarily to the Nucleus accumbens (NAc) brain region; The two groups of IC-projected neurons do not overlap
each other anatometrically.

2.

With the help of optogenetics and in vivo fiber recording technology, researchers found that IC-CeA projects neurons to store and express fear memories, encoding negative emotions; IC-NAc projects neurons to store and express regressive memories, encoding positive emotions
.

In terms of intrinsic physiological properties, the researchers found that IC-CeA, which is responsible for encoding fear emotion, projected higher excitability in the basal state of neurons, providing supporting evidence
for understanding the firmness of negative emotions associated with fear memories.

More interestingly, there is also an interactive inhibition of memory behavior-dependent interaction between IC-CeA and IC-NAc projection neuron clusters, which constitutes a loop mechanism
for the body to switch positive and negative emotions.

3.
Identify positive and negative emotions with one click to convert new targets

With the help of reverse transunisynaptic tracing technology, the researchers tracked the upper level neurons of two IC-projected neuronal clusters throughout the brain, and found that the frontal cortex responsible for advanced cognitive functions (such as orbitofrontal cortex, OFC) exercised top-down bias control over clusters of IC regressive memory neurons, thereby selectively driving the expression
of specific memories.

In summary, this study identified the neuronal clusters responsible for positive and negative emotions within the IC, and established the organizational rules of the multi-stage loop coordinated control of the opposite emotional memory neuron clusters within the cortex that rely on different subcortical pathways and are simultaneously controlled by the frontal cortex "top-down", providing a new understanding for understanding
the neural loop calculation principle of emotional dynamic transformation.

Illustration: "Intercortic-intracortic-subcortical" loop organization in
the distributed storage of fear and regression memory.

Wang Qi, a postdoctoral fellow at Shanghai Jiao Tong University School of Basic Medicine, and Zhu Jiajie, an undergraduate student majoring in biomedical sciences at Zhiyuan University, are co-first authors
of the paper.

Li Weiguang, a researcher at the Institute of Brain Science Translation, Fudan University, Siyu Zhang, and Professor Xu Tianle of the School of Basic Medicine of Shanghai Jiao Tong University are co-corresponding authors
of the paper.

References

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