Neuron. Dr. Zhang Xiangyu reveals that eliminating fear is its own reward.

It's definitely a positive feeling when you expect a very bad experience to happen and then it doesn't happen.so what does our brain go through behind this? On January 14, 2020, MIT, led by Nobel laureate Susumu Tonegawa (the first author is Dr. Zhang Xiangyu) published a long article "Amy gdala reward nerves form and store fear extension" on neuron New research on fear elimination training in mice reveals the underlying neural mechanism: the same neurons responsible for encoding rewards form new memories to suppress fear memory.this study specifically shows that fear extinction memory and reward are stored by a group of reward neurons expressing specific genes in the basolateral amygdala (BLA).it is well known that our emotional state is controlled by a tiny brain structure called amygdala located in the dorsomedial part of the anterior temporal lobe, slightly forward of the top of the hippocampus and inferior horn of the lateral ventricle.it is responsible for the generation, identification and regulation of emotions. Positive emotions such as happiness and negative emotions such as fear and anxiety are crucial to the formation and regulation of emotional behavior and memory.as early as 2016, Tonegawa research team found that there are two different gene types of neurons in Bla [1]: the neurons expressing ppp1r1b gene in the posterior bla (PBLA) encode positive emotion and memory, while the neurons in the anterior half of bla (anti BLA) encode positive emotion and memory The rspo2 expressing neurons encode negative emotion and memory, and the two types of neurons compete with each other.in this latest study, as the first author of this paper, Zhang Xiangyu, a graduate student at the tonggawa laboratory, set out to investigate whether this competitive balance of neural circuits also constitutes the basis for fear memory and its demise.in order to test this hypothesis, the author adopts the classical contextual fear conditioning and extention learning paradigm: mice are made to form fear memory in specific environment by electric shock.the next day, the mice were put back in the same environment for 45 minutes, but no electrical stimulation was given, so that they could form new memories of the environment without fear.this process is called fear extention training.in this process, the authors first detected the activity of ppp1r1b neurons and rspo2 expressing neurons in two different ways: detection and in vivo calcium imaging.they found that after fear memory elimination training, positive neurons expressing ppp1r1b were significantly activated, while negative neurons expressing rspo2 were inhibited.due to the elimination of fear memory, new memory will be formed to suppress the initial fear memory.memory is stored in a group of neurons, called memory engram.therefore, using the technology previously developed by the Tonegawa team, researchers have further discovered the trace cells that store the fear elimination memory: by activating these trace cells of fear elimination memory through optogenetics, the process of fear elimination can be promoted and accelerated; when these neurons are inhibited, the initial fear memory cannot be eliminated, even if tested The mice were trained to eliminate fear memory.finally, the researchers wanted to explore the relationship between these fear eliminating memory traces and those responsible for positive emotion perception in the amygdala neurons expressing ppp1r1b.they found that the two groups of nerve cells overlapped to a large extent, and had the same behavioral function: activating the neurons of fear elimination memory through photogenetics could make mice produce pleasant feeling; conversely, activating neurons that sense positive emotions through photogenetics could help mice with fear memory elimination training.this study not only identified an accurate population of brain cells that are key to learning to stop feeling afraid, but also further demonstrated that these neurons are neurons that help encode reward.this discovery not only provides a further scientific and theoretical support for cognitive behavioral therapy (exposure behavior therap) currently used in clinical practice, but also helps to promote drug targets for post-traumatic stress disorder (PTSD) or anxiety disorder by identifying their exact location in the brain and their unique gene expression. Kim, J., Pignatelli, M., Xu, S., itohara, S., and Tonegawa, S. (2016). Antioxidant negative and positive nerves of the basolatal amygdala. NAT. Neurosci. 19, 1636 – 1646