MITのPicower Institute for Learning and Memoryの科学者が1月14日にNeuronで発表したこの研究は、恐怖の絶滅の記憶と報酬の感覚が、扁桃体後部(pBLA)の遺伝子Ppp1r1bを発現するニューロンによって同様に保存されることを具体的に示しています、嫌悪感ややりがいのある感情、または「バレンス」と記憶との関連付けを割り当てることが知られている地域。この研究は、大学院生のシャン・ギュー、元大学院生のジョシュア・キム、および理研-MITの生物学と神経科学の教授、利根川進、MITおよびハワードのピコワー学習および記憶研究所の神経回路遺伝学研究所によって実施されました。
January 15, 2020
With these neurons, extinguishing fear is its own reward
When you expect a really bad experience to happen and then it doesn’t, it’s a distinctly positive feeling. A new study of fear extinction training in mice may suggest why: The findings not only identify the exact population of brain cells that are key for learning not to feel afraid anymore, but also show these neurons are the same ones that help encode feelings of reward.
The study, published Jan. 14 in Neuron by scientists at MIT’s Picower Institute for Learning and Memory, specifically shows that fear extinction memories and feelings of reward alike are stored by neurons that express the gene Ppp1r1b in the posterior of the basolateral amygdala (pBLA), a region known to assign associations of aversive or rewarding feelings, or “valence,” with memories. The study was conducted by Xiangyu Zhang, a graduate student, Joshua Kim, a former graduate student, and Susumu Tonegawa, Professor of Biology and Neuroscience at RIKEN-MIT Laboratory of Neural Circuit Genetics at the Picower Institute for Learning and Memory at MIT and Howard Hughes Medical Institute.
“We constantly live at the balance of positive and negative emotion,” Tonegawa said. “We need to have very strong memories of dangerous circumstances in order to avoid similar circumstances to recur. But if we are constantly feeling threatened we can become depressed. You need a way to bring your emotional state back to something more positive.”
Above: In the basolateral amygdala of a mouse, Ppp1r1b-expressing cells are stained green, while the cells in a fear extinction memory engram appear red.
Overriding fear with reward
In a prior study, Kim showed that Ppp1r1b-expressing neurons encode rewarding valence and compete with distinct Rspo2-expressing neurons in the BLA that encode negative valence. In the new study, Zhang, Kim and Tonegawa set out to determine whether this competitive balance also underlies fear and its extinction.
In fear extinction, an original fearful memory is thought to be essentially overwritten by a new memory that is not fearful. In the study, for instance, mice were exposed to little shocks in a chamber, making them freeze due to the formation of fearful memory. But the next day, when the mice were returned to the same chamber for a longer period of time without any further little shocks, freezing gradually dissipated and hence this treatment is called fear extinction training. The fundamental question then is whether the fearful memory is lost or just suppressed by the formation of a new memory during the fear extinction training.
While the mice underwent fear extinction training the scientists watched the activity of the different neural populations in the BLA. They saw that Ppp1r1b cells were more active and Rspo2 cells were less active in mice that experienced fear extinction. They also saw that while Rspo2 cells were mostly activated by the shocks and were inhibited during fear extinction, Ppp1r1b cells were mostly active during extinction memory training and retrieval, but were inhibited during the shocks.