{"title":"Environment impacts sexual preference: dopamine sends signals under pressure to decide which sex you like","authors":"Rou Li, Lin Liu, Min Wu","doi":"10.1038/s41392-025-02211-0","DOIUrl":null,"url":null,"abstract":"<p>A study by Wei et al. in <i>Science</i> identified a unique sexual binary neural circuit encoding a sexual preference switch, known as the ventral tegmental area dopaminergic (VTA<sup>DA</sup>) circuit, which exhibits a preference for female social interactions among both sex mice, but switches to male preferences when confronted with survival threats (Fig. 1).<sup>1</sup></p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 1</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41392-025-02211-0/MediaObjects/41392_2025_2211_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"816\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41392-025-02211-0/MediaObjects/41392_2025_2211_Fig1_HTML.png\" width=\"685\"/></picture><p><b>a</b> Schematic diagram illustrating the social preference test. Both male and female mice exhibited a preference for social interaction with females. However, this preference shifted to male preference when facing survival threats (TMT, contextual FC, or cued FC). <b>b</b> The sexually dimorphic DA circuits involve the sociosexual preferences of females and males. C-Fos staining revealed that the activity changes in VTA<sup>DA</sup> and their downstream circuits, the mPOA and the NAc, are closely related to these changes. A calcium signaling fiber optic recording method for real-time monitoring of VTA<sup>DA</sup> neural activity during social processes, along with a chemical genetics approach for activating VTA<sup>DA</sup> neurons. Dual-color calcium signal fiber recording combined with viral tracing for synchronous monitoring of VTADA neuronal subpopulation activity. Chemical genetic methods were employed to manipulate the VTA<sup>DA</sup>-mPOA and VTA<sup>DA</sup>-NAc projection. The competitive balance between VTA<sup>DA</sup>-NAc and the defense loop VTA<sup>DA</sup>-mPOA determines the social preferences of male animals. By employing optogenetic techniques, the VTA-NAc projection was stimulated with light in both tonic and phasic discharge modes. Female individuals selectively regulate downstream neurons by modulating firing patterns in the VTA<sup>DA</sup>-NAC) ultimately shaping their social preferences. TMT trimethylthiazoline, FC fear conditioning, VTA ventral tegmental area, mPOA midbrain preoptic area, NAc nucleus accumbens, CNO clozapine N-oxide, D1R type 1 DA receptor, D2R type 2 DA receptor. This figure was created with BioRender.com</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"6 1","pages":""},"PeriodicalIF":40.8000,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Signal Transduction and Targeted Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41392-025-02211-0","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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Abstract
A study by Wei et al. in Science identified a unique sexual binary neural circuit encoding a sexual preference switch, known as the ventral tegmental area dopaminergic (VTADA) circuit, which exhibits a preference for female social interactions among both sex mice, but switches to male preferences when confronted with survival threats (Fig. 1).1
Fig. 1
a Schematic diagram illustrating the social preference test. Both male and female mice exhibited a preference for social interaction with females. However, this preference shifted to male preference when facing survival threats (TMT, contextual FC, or cued FC). b The sexually dimorphic DA circuits involve the sociosexual preferences of females and males. C-Fos staining revealed that the activity changes in VTADA and their downstream circuits, the mPOA and the NAc, are closely related to these changes. A calcium signaling fiber optic recording method for real-time monitoring of VTADA neural activity during social processes, along with a chemical genetics approach for activating VTADA neurons. Dual-color calcium signal fiber recording combined with viral tracing for synchronous monitoring of VTADA neuronal subpopulation activity. Chemical genetic methods were employed to manipulate the VTADA-mPOA and VTADA-NAc projection. The competitive balance between VTADA-NAc and the defense loop VTADA-mPOA determines the social preferences of male animals. By employing optogenetic techniques, the VTA-NAc projection was stimulated with light in both tonic and phasic discharge modes. Female individuals selectively regulate downstream neurons by modulating firing patterns in the VTADA-NAC) ultimately shaping their social preferences. TMT trimethylthiazoline, FC fear conditioning, VTA ventral tegmental area, mPOA midbrain preoptic area, NAc nucleus accumbens, CNO clozapine N-oxide, D1R type 1 DA receptor, D2R type 2 DA receptor. This figure was created with BioRender.com
期刊介绍：
Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy.
Scope: The journal covers research on major human diseases, including, but not limited to:
Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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