Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus.

Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus.
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DOI:
10.1038/nature13169
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发表时间:
2014-05-29
期刊:
影响因子:
64.8
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--
中科院分区:
综合性期刊1区
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社会行为(例如侵略或交配)进行了一系列与唤醒水平增加有关的开胃菜和完整阶段。这种升级是如何在大脑中编码的,并且与行为作用选择有关,仍然是神经科学中的重要问题。鼠腹侧下丘脑(VMHVL)的腹外侧细分包含神经元,其活性在男性和男女社会相遇期间增加。该区域的非细胞类型特异性光遗传激活引起了攻击行为,但没有安装。我们已经确定了以雌激素受体1(ESR1)为标志的VMHVL神经元的子集,并研究了它们在男性社会行为中的作用。光遗传操作表明ESR1+(但不是ESR1-)神经元足以引发攻击,并且在持续的激动行为期间,它们的活性是不断需要的。令人惊讶的是,这些神经元的弱光遗传激活促进了对男性和女性的越来越多的行为,而不是攻击,以及嗅探和仔细研究(CI)。在一次社会遭遇中,增加的光刺激强度可以促进从CI和安装到攻击的过渡。重要的是,时间分辨的光遗传学抑制实验揭示了对社会相互作用的食用(调查)和完整阶段中ESR1+神经元的要求。在体外的光遗传激活和钙成像实验以及体内的C-FOS分析表明,增加的光刺激强度增加会增加活性神经元的数量和每个神经元的平均活性水平。这些数据表明,VMHVL中的ESR1+神经元控制着社会相遇从其食欲到其完整阶段的发展,以一种可扩展的方式反映了人群中活性神经元的数量或类型。
Social behaviors, such as aggression or mating, proceed through a series of appetitive and consummatory phases that are associated with increasing levels of arousal. How such escalation is encoded in the brain, and linked to behavioral action selection, remains an important unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male-male and male-female social encounters. Non-cell type-specific optogenetic activation of this region elicited attack behavior, but not mounting. We have identified a subset of VMHvl neurons marked by the estrogen receptor 1 (Esr1), and investigated their role in male social behavior. Optogenetic manipulations indicated that Esr1+ (but not Esr1-) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behavior. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behavior, rather than attack, towards both males and females, as well as sniffing and close investigation (CI). Increasing photostimulation intensity could promote a transition from CI and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1+ neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1+ neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population.