小柯机器人

美国哈佛医学院Andermann, Mark L.课题组的一项最新研究表明，下丘脑多巴胺神经元通过持续激活cAMP信号通路调控交配行为。相关论文于2021年8月25日在线发表在《自然》杂志上。

研究人员探究了交配诱导的多巴胺能机制及其在雄性小鼠中的持久性。与雌性小鼠的短暂接触会在数十分钟内激发雄性的交配兴趣，而一次成功的交配会引发饱腹感，随后在几天内逐渐消退。研究人员发现这两个过程都由下丘脑前腹侧和视前室周围(AVPV/PVpo)特异的多巴胺神经元控制。在观察雌性的过程中，多巴胺会在内侧视前区(MPOA)中短暂释放，该区域对交配行为至关重要。MPOA中AVPV/PVpo多巴胺轴突的光遗传学刺激揭示了雌性诱导的启动效应。

使用光学和分子方法来跟踪和操纵细胞内信号，研究人员发现这种启动效应依赖于环磷酸腺苷水平和蛋白激酶A活性的增加，这导致MPOA中与交配相关多巴胺信号的积累。MPOA中的多巴胺瞬变在成功交配后被消除，这可能会造成禁欲。与此一致，抑制AVPV/PVpo多巴胺神经元选择性降低了雄性的交配动力，而刺激这些神经元可以恢复性饱后交配的冲动。综上，该研究表明多巴胺神经元特异性信号的积累或抑制可调节数分钟和数天的交配行为。

据悉，瞬时神经调节可对神经回路和活跃状态产生长期影响。

附：英文原文

Title: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling

Author: Zhang, Stephen X., Lutas, Andrew, Yang, Shang, Diaz, Adriana, Fluhr, Hugo, Nagel, Georg, Gao, Shiqiang, Andermann, Mark L.

Issue&Volume: 2021-08-25

Abstract: Transient neuromodulation can have long-lasting effects on neural circuits and motivational states1,2,3,4. Here we examine the dopaminergic mechanisms that underlie mating drive and its persistence in male mice. Brief investigation of females primes a male’s interest to mate for tens of minutes, whereas a single successful mating triggers satiety that gradually recovers over days5. We found that both processes are controlled by specialized anteroventral and preoptic periventricular (AVPV/PVpo) dopamine neurons in the hypothalamus. During the investigation of females, dopamine is transiently released in the medial preoptic area (MPOA)—an area that is critical for mating behaviours. Optogenetic stimulation of AVPV/PVpo dopamine axons in the MPOA recapitulates the priming effect of exposure to a female. Using optical and molecular methods for tracking and manipulating intracellular signalling, we show that this priming effect emerges from the accumulation of mating-related dopamine signals in the MPOA through the accrual of cyclic adenosine monophosphate levels and protein kinase A activity. Dopamine transients in the MPOA are abolished after a successful mating, which is likely to ensure abstinence. Consistent with this idea, the inhibition of AVPV/PVpo dopamine neurons selectively demotivates mating, whereas stimulating these neurons restores the motivation to mate after sexual satiety. We therefore conclude that the accumulation or suppression of signals from specialized dopamine neurons regulates mating behaviours across minutes and days.

DOI: 10.1038/s41586-021-03845-0

Source: https://www.nature.com/articles/s41586-021-03845-0

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