Neuron

评语： 

本文利用化学遗传学兴奋雄鼠的PVH 催产素神经元，发现攻击幼鼠行为相关的脑区PeFA中cfos信号的显著减少，这个现象与行为学相一致。在后文中作者发现LH与抑制攻击幼鼠行为有关，我很好奇PeFA与LH是否具有协同作用。同时本文利用rabies virus逆向示踪的方法筛选发生环路可塑性变化的上游脑区，这种方法虽然新颖但其敏感性和可靠性需要更多的检验。直接兴奋LH ÚPVH环路仅能看到微弱的行为学效应，可能通过增强该环路的突触传递才能看到更明显的行为学效应。

关键词： 

PVH, oxytocin, parental behavior, aggression, LH

文章链接DOI： 

https://doi.org/10.1016/j.neuron.2022.03.033

Abstract

The adult brain can flexibly adapt behaviors to specific life-stage demands. For example, while sexually naïve male mice are aggressive to the conspecific young, they start to provide caregiving to infants around the time when their own young are expected. How such behavioral plasticity is implemented at the level of neural connections remains poorly understood. Here, using viral-genetic approaches, we establish hypothalamic oxytocin neurons as the key regulators of the parental caregiving behaviors of male mice. We then use rabies-virus-mediated unbiased screening to identify excitatory neural connections originating from the lateral hypothalamus to the oxytocin neurons to be drastically strengthened when male mice become fathers. These connections are functionally relevant, as their activation suppresses pup-directed aggression in virgin males. These results demonstrate the life-stage associated, long-distance, and cell-type-specific plasticity of neural connections in the hypothalamus, the brain region that is classically assumed to be hard-wired.

iScience

评语： 

本文选择了群居性和非群居性的两个小鼠品系来研究小鼠与性无关的社交行为（同性社交行为），使得社交行为的研究更能排除个体差异的影响。结果发现不同品系小鼠的VTA TH神经元对社交行为的响应是有差异的，而PVH 催产素神经元则没有品系间的差异，提示奖赏环路在社交行为中的关键作用。本文为社交牛逼症和社交恐惧的个体差异提供了线索。不过文中主要结论来自于cfos染色得出的相关性，需要更多的因果性的研究证据支持。

关键词： 

PVH, oxytocin, social behavior, VTA, cfos

文章链接 ： 

https://doi.org/10.1016/j.isci.2022.104230

Abstract

We investigated whether nonreproductive social interactions may be rewarding for colonial but not non-colonial species. We found that the colonial spiny mouse (Acomys cahirinus) is significantly more gregarious, more prosocial, and less aggressive than its non-colonial relative, the Mongolian gerbil (Meriones unguiculatus). In an immediate-early gene study, we examined oxytocin (OT) and tyrosine hydroxylase (TH) neural responses to interactions with a novel, same-sex conspecific or a novel object. The paraventricular nucleus of the hypothalamus (PVN) OT cell group was more responsive to interactions with a conspecific compared to a novel object in both species. However, the ventral tegmental area (VTA) TH cell group showed differential responses only in spiny mice. Further, PVN OT and VTA TH neural responses positively correlated in spiny mice, suggesting functional connectivity. These results suggest that colonial species may have evolved neural mechanisms associated with reward in novel, nonreproductive social contexts

to promote large group-living.

Neuroscience

评语： 

本文的实验严谨地证明了OXTR S216的磷酸化对于大鼠长时程社交记忆的维持是不可或缺的，并且发现人类存在OXTR S216位点的单核苷酸多态性，这可能为解释人类社交能力的多态性提供新的角度。由于转基因工具大鼠的限制，文中敲除PKD1的相关实验是在PKD1^flox/flox小鼠中进行。作者发现小鼠的长时程社交记忆维持的时间窗明显短于大鼠。我很好奇这种品系的差异是否与OXTR相关，比如其表达量、或者磷酸化水平的差异，但文中的讨论部分没有涉及这个问题。

关键词： 

Phosphorylation, OXTR, PKD1, LTSM (long term social memory)

文章链接： 

https://www.science.org/doi/10.1126/scisignal.abd0033?url_ver=Z39.882003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Abstract

Social memory enables one to recognize and distinguish specific individuals. It is fundamental to social behaviors that can be mediated by the oxytocin receptor (OXTR), such as forming relationships. We investigated the molecular regulation and function of OXTR in animal behavior involving social memory. We found that Ser261 in OXTR was phosphorylated by protein kinase D1 (PKD1). Neuronal Ca2+ signaling and behavior analyses revealed that rats expressing a mutated form of OXTR that cannot be phosphorylated at this residue (OXTR S261A) in the medial amygdala (MeA) exhibited impaired long-term social memory (LTSM). Blocking the phosphorylation of wild-type OXTR in the MeA using an interfering peptide in rats or through conditional knockout of Pkd1 in mice reduced

social memory retention, whereas expression of a phosphomimetic mutant of OXTR rescued it. In HEK293A cells, the PKD1-mediated phosphorylation of OXTR promoted its binding to Gq protein and, in turn, OXTR-mediated phosphorylation of PKD1, indicating a positive feedback loop. In addition, OXTR with a single-nucleotide polymorphism found in humans (rs200362197), which has a mutation in the conserved recognition region in the PKD1 phosphorylation site, showed impaired activation and signaling in vitro and in HEK293A cells similar to that of the S216A mutant. Our findings describe a phosphoregulatory loop for OXTR and its critical role in social behavior that might be further explored in associated disorders.