Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling.
Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling.
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下丘脑多巴胺神经元通过持续的cAMP信号激发交配。
DOI：
10.1038/s41586-021-03845-0
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发表时间：
2021-09
期刊：
影响因子：
64.8
通讯作者：
Andermann ML
中科院分区：
文献类型：
--
作者：
Zhang SX;Lutas A;Yang S;Diaz A;Fluhr H;Nagel G;Gao S;Andermann ML
瞬时神经调节可以对神经回路和动机状态产生长期影响。我们研究了多巴胺能机制的基础交配驱动和持久性在雄性小鼠。对雌性的简短调查引发了雄性数十分钟的交配兴趣，而一次成功的交配引发了几天后逐渐恢复的饱腹感。我们发现，这两个过程是由专门的前腹侧和视前室周（AVPV/PVpo）多巴胺神经元在下丘脑。在雌性的研究中，多巴胺在内侧视前区（MPOA）短暂释放，这是一个对交配行为至关重要的区域。MPOA中AVPV/PVpo多巴胺轴突的光遗传刺激再现了女性暴露的启动效应。使用光学和分子方法跟踪和操纵细胞内信号，我们表明，这种引发效应出现从交配相关的多巴胺信号的MPOA通过环磷酸腺苷（cAMP）水平和蛋白激酶A（PKA）活性的累积。MPOA中的多巴胺瞬变在成功交配后被消除，可能确保禁欲。与这个想法一致，抑制AVPV/PVpo多巴胺神经元选择性地使交配失去动力，而刺激这些神经元在性满足后恢复交配的动机。因此，来自专门多巴胺神经元的信号的积累或抑制在几分钟和几天内调节交配行为。
Transient neuromodulation can have long-lasting effects on neural circuits and motivational states. We examined dopaminergic mechanisms underlying mating drive and its persistence in male mice. Brief investigation of females primes a male’s interest to mate for tens of minutes, while a single successful mating triggers satiety that gradually recovers over days. We found that both processes are controlled by specialized anteroventral and preoptic periventricular (AVPV/PVpo) dopamine neurons in the hypothalamus. During investigations of females, dopamine is transiently released in the medial preoptic area (MPOA), an area critical for mating behaviors. Optogenetic stimulation of AVPV/PVpo dopamine axons in the MPOA recapitulates the priming effect of female exposure. Using optical and molecular methods for tracking and manipulating intracellular signaling, we show that this priming effect emerges from accumulation of mating-related dopamine signals in the MPOA via accrual of cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity. Dopamine transients in the MPOA are abolished following a successful mating, likely ensuring abstinence. Consistent with this idea, inhibiting AVPV/PVpo dopamine neurons selectively demotivates mating, while stimulating these neurons restores the motivation to mate following sexual satiety. Therefore, accumulation or suppression of signals from specialized dopamine neurons regulates mating behaviors across minutes and days.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
64.8
作者：
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Anderson DJ
影响因子：
4.2
作者：
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通讯作者：
Yellen, Gary
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
影响因子：
15.9
作者：
Krashes, Michael J.;Koda, Shuichi;Lowell, Bradford B.
通讯作者：
Lowell, Bradford B.