Dual roles of anterior cingulate cortex neurons in pain and pleasure in adult mice
Human and animal studies indicate that some brain regions are activated during painful and pleasant situations, such as the anterior cingulate cortex (ACC). In the present study, we wanted to determine if some of the same neurons in the ACC may be activated by both pain and pleasure. We labeled neurons activated by two stimuli by using two immediate early genes (IEGs), Arc and Homer1a, and detected the intranuclear transcription of the IEG mRNA in situ. We found that there are double-labeling neurons in the ACC after the mice received pain and sexual attraction stimulation. The double-labeling ACC neurons were higher in male mice exposed to female mice (attractive stimulus) than the group exposed to male mice (normal stimulus). The IEG, which indicates the sexual attraction, were also higher in the female exposing group, while the IEG indicating pain showed no significant variance between two groups. Our findings suggest that ACC neurons play important roles in the process of both pain and pleasure.
KeywordsIEG ACC Arc Homer1a Pain Sexual attraction
Anterior cingulate cortex
Cellular compartment analysis of temporal activity by fluorescent in situ hybridization
Immediate early gene
Pain and pleasure are two major experiences in human and animals. We often pursue pleasure, while avoiding pain. The relationship between pain and pleasure can be further demonstrated by the analgesic effect of pleasure. Palatable food, pleasant odor, pleasurable music and sexual behavior were all found to reduce pain . More interestingly, in certain conditions, pleasure can be gained by enduring pain, such as enjoying a spicy hotpot or receiving a massage. The central mechanism for pleasure is less investigated than the mechanism for pain, which has received more attention [2, 3]. The ACC is well known to participate in pain sensation and nociceptive processing [4, 5, 6, 7]. Less has been studied about the ACC’s relationship to pleasure or happiness. It has been reported that the ACC is activated when a man views the picture of his lover . Wu et al. has reported that ACC neurons of male mice could be activated after exposed to female mice . However, it is unclear if pain or pleasure are processed through different population of neurons, or if some ACC neurons may contribute to both pain and pleasure.
CatFISH serves as a functional imaging that allows investigators to distinguish neuronal populations activated by two distinct stimuli. The IEGs such as Arc, Homer1a, zif268 and c-fos, were used in catFISH. Among them, the Arc/Homer1a catfish method is a useful tool [10, 11, 12]. In this study, we used the Arc/Homer1a catFISH to distinguish two (pain and sexual attraction) stimuli and to identify ACC neurons that are activated by both stimuli.
In conclusion, by applying the Arc/Homer1a catFISH, we discovered that neurons encoding pain and sexual attraction information can be co-labeled in the same neurons of the ACC, which may indicate that pain and sexual attraction may be processed by some of the same neurons in the ACC. The molecular and synaptic mechanism still require further investigation.
The authors would like to thank Masanori Nomoto for the guidance of catFISH work. We also thank Fang Yue and Yong-Ming Liu for their contributions to the study.
This work was partially supported by grants from the CIHR project grant (PJT-148648) awarded to MZ.
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Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
JSL and QYC designed and performed the experiments then analyzed the data. KI provided plasmids containing Arc/Homer1a cDNA. SBZ also participated in the experiments. JSL, QYC and MZ drafted the manuscript and finished the final version of the manuscript. All authors read and approved the final manuscript.
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