Neuron. The Luo Minmin team revealed the neural loop mechanism by which mid-seam nucleus dopamine neurons regulate the reward-related memory expression.

Learning and memory are the most important abilities for all animals to adapt to complex environments.through learning, we can connect things that are not related to each other.the memory produced in this learning process is called associative memory.the formation and expression of associative memory widely exist in our daily life and affect our behavior choice.for example, the idiom "love my house and love my dog", and once bitten by a snake and afraid of the well rope for ten years, are typical examples of related memory.abnormal expression of associative memory is the main cause of many mental diseases, such as post-traumatic stress disorder, depression, drug addiction, etc.the study of associative memory, especially the expression of associative memory, is of great significance for us to understand the operation of our own brain to external stimuli and the treatment of related diseases.on March 6, 2020, Luo Minmin Laboratory of Beijing Institute of life sciences published a research paper entitled "the raphe dopamine system controls the expression of intentional memory" in the journal Neuron.this study found that a group of dopamine neurons located in the dorsal raphe nucleus control the expression of reward and punishment related memory, and revealed the neural loop mechanism of its regulation of reward related memory expression.memory formation (learning) and expression are controlled by multiple nuclei in the brain.these nuclei receive a large amount of dopaminergic input.previous studies have shown that dopamine system, especially dopamine neurons in nucleus accumbens, drives learning and memory, especially reward related memory.and whether dopamine system is involved in memory expression is not clear.the researchers noticed that there were also a number of dopamine neurons in the dorsal raphe nucleus of the midbrain.compared with the dopaminergic neurons in the nucleus accumbens, the number of dopaminergic neurons in the dorsal raphe nucleus (DRN) is relatively small, and has been considered as an extension of dopaminergic neurons in nucleus accumbens by some previous studies, and these neurons have been neglected for a long time.its behavioral function, especially whether it participates in the process of learning and memory, is not clear.using the single cell reconstruction technology developed earlier, the researchers described the morphological characteristics of dopaminergic neurons in the dorsal raphe nucleus in detail, and confirmed that the dopamine neurons in the dorsal raphe nucleus were a special group of midbrain dopamine neurons independent of the dopamine neurons in the nucleus accumbens, and mainly projected to the bed nucleus of the striatum terminalis and the middle part of the amygdala. using in vivo fiber recording technology, the researchers found that these dopaminergic neurons in the dorsal raphe nucleus can be activated by reward and punishment. interestingly, the stimulation related to reward or punishment can also activate dopaminergic neurons in the dorsal raphe nucleus, suggesting that these neurons may be involved in learning and memory. Figure 1. The dopaminergic neurons in the dorsal raphe nucleus (DRN) encode reward and punishment information. Researchers specifically damaged or inhibited the dopaminergic neurons in the dorsal raphe nucleus, and found that the absence of dopamine neurons in the dorsal raphe nucleus significantly affected the expression of memory related to food reward or electric shock punishment. these neurons are also involved in the regulation of opioid addiction related memory expression: when the addicted mice enter the morphine related environment, the activity of dopamine neurons in the dorsal raphe nucleus increases; damage or inhibition of these neurons significantly affects the expression of opioid pleasure or withdrawal related memory. Figure 2 Dopaminergic neurons in the dorsal raphe nucleus regulate the expression of memory. In order to confirm whether the behavioral function of dopaminergic neurons in the dorsal raphe nucleus is mediated by the dopamine neurotransmitter released by the dopamine neurotransmitter released by the dopamine neurons in the dorsal raphe nucleus, the researchers used the newly developed genetic coding dopamine fluorescence probe in the Li Yulong Laboratory of Peking University, combined with in vivo optical fiber recording technology, for the first time in the two downstream nuclei of the dorsal raphe nucleus Dopamine release induced by reward and punishment was detected in bed nucleus and central amygdala. on this basis, the expression of reward and punishment memory and opioid addiction memory of experimental mice were significantly affected by the in vivo gene editing technology of crispr-cas9 mediated by adeno-associated virus, which proved that dopamine neurotransmitter signal from dorsal raphe nucleus plays an important role in regulating memory expression. Fig. 3. Dopamine released by dopamine neurons in dorsal raphe nucleus is very important for memory expression. Further, the researchers used morphine as the breakthrough point and used rabies virus based screening method to identify a neural pathway from glutamatergic neurons in the lateral parabrachial nucleus to dopaminergic neurons in dorsal raphe nucleus. morphine intake significantly increased the excitability of glutamatergic neurons in the lateral parabrachial nucleus projecting to the dorsal raphe nucleus, thus enhancing the connection of this neural pathway. behavioral experiments show that this neural pathway specifically regulates the expression of reward related memory: inhibition of this pathway by neurotoxin or chemical genetics can block the expression of food related memory and morphine intake pleasure related memory; inhibition of this pathway also destroys the coding of reward information by dopaminergic neurons in dorsal raphe nucleus. Fig. 4. The pathway from glutamatergic neurons in the lateral parabrachial nucleus to dopaminergic neurons in the dorsal raphe nucleus regulates the expression of reward memory. This systematic study reveals the neural loop mechanism of regulating memory expression, deepens our understanding of the function of dopamine system, and provides new ideas for the treatment of drug addiction. Dr. Lin Rui and Dr. Liang Jingwen from Luo Minmin Laboratory of Beijing Institute of life sciences are co authors of this paper. Other authors of this paper include Wang Ruiyu, Yan Ting, Zhou Yutong, Liu Yang and Feng qiru of Luo Minmin laboratory, Dr. Sun Fangmiao and Dr. Li Yulong of Peking University, and Dr. Li an and Professor Gong Hui of Huazhong University of science and technology. Dr. Lin Rui and Dr. Luo Minmin are co authors of this paper. original link: plate maker: Qi sauce