Oxytocin receptors are widely distributed in the prairie vole (Microtus ochrogaster) brain: Relation to social behavior, genetic polymorphisms, and the dopamine system.

Oxytocin receptors are widely distributed in the prairie vole (Microtus ochrogaster) brain: Relation to social behavior, genetic polymorphisms, and the dopamine system.
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DOI:
10.1002/cne.25382
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发表时间:
2022-11
影响因子:
2.5
通讯作者:
Young, Larry J.
Young, Larry J.
中科院分区:
医学3区
文献类型:
--
作者:
Inoue, Kiyoshi;Ford, Charles L.;Horie, Kengo;Young, Larry J.

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催产素通过直接调节神经元、调节神经网络活动以及与其他神经递质系统的相互作用来调节社会行为。催产素信号传导的行为效应由大脑催产素受体的物种特异性分布决定。实行一夫一妻制的草原田鼠是一种有用的模式生物,可以用来阐明催产素在社会行为中的作用,包括配对关系、对社会损失的反应和安慰。然而,目前还没有对整个草原田鼠大脑中表达催产素受体的细胞进行全面的定位。在这里,我们采用了高度灵敏的原位杂交 RNAscope 来构建催产素受体 mRNA 表达细胞的详尽全脑图谱。我们发现催产素受体 mRNA 表达广泛且弥散在整个大脑中,特定区域表现出特别强烈的表达。比较受体与 mRNA 的结合发现,海马和黑质区域含有催产素受体蛋白,但缺乏 mRNA,表明催产素受体可以转运到远端神经元过程,与突触前催产素受体功能一致。在伏核(涉及催产素依赖性社会联系的区域)中,在表达 D1 和 D2 多巴胺受体的细胞亚型中均检测到催产素受体 mRNA 表达。此外,自然遗传多态性强烈影响伏隔核 D1 和 D2 受体细胞类型中催产素受体的表达。总的来说,我们的研究结果进一步阐明了催产素信号能够在多大程度上影响全脑神经活动、对社会刺激的反应和社会行为。使用 RNAscope 原位杂交,我们全面绘制了整个草原田鼠大脑中催产素受体 mRNA 的图谱。 mRNA 和蛋白质定位的比较揭示了局部不匹配,表明 OXTR 具有突触前和突触后功能。还检查了 Oxtr mRNA 与伏隔核中 D1/D2 受体的共表达。
Oxytocin regulates social behavior via direct modulation of neurons, regulation of neural network activity, and interaction with other neurotransmitter systems. The behavioral effects of oxytocin signaling are determined by the species-specific distribution of brain oxytocin receptors. The socially monogamous prairie vole has been a useful model organism for elucidating the role of oxytocin in social behaviors, including pair bonding, response to social loss, and consoling. However, there has been no comprehensive mapping of oxytocin receptor-expressing cells throughout the prairie vole brain. Here, we employed a highly sensitive in situ hybridization, RNAscope, to construct an exhaustive, brain-wide map of oxytocin receptor mRNA-expressing cells. We found that oxytocin receptor mRNA expression was widespread and diffuse throughout the brain, with specific areas displaying particularly robust expression. Comparing receptor binding with mRNA revealed that regions of the hippocampus and substantia nigra contained oxytocin receptor protein but lacked mRNA, indicating that oxytocin receptors can be transported to distal neuronal processes, consistent with presynaptic oxytocin receptor functions. In the nucleus accumbens, a region involved in oxytocin-dependent social bonding, oxytocin receptor mRNA expression was detected in both the D1 and D2 dopamine receptor-expressing subtypes of cells. Furthermore, natural genetic polymorphisms robustly influenced oxytocin receptor expression in both D1 and D2 receptor cell types in the nucleus accumbens. Collectively, our findings further elucidate the extent to which oxytocin signaling is capable of influencing brain-wide neural activity, responses to social stimuli, and social behavior. Using RNAscope in situ hybridization, we comprehensively mapped oxytocin receptor mRNA throughout the prairie vole brain. Comparison of mRNA and protein localization revealed localized mismatches suggesting both pre- and post-synaptic function for OXTRs. Co-expression of Oxtr mRNA with D1/D2 receptors in the nucleus accumbens was also examined.
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发表时间: 2021-08
期刊: Nature
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DOI: 10.1038/s41582-021-00602-9
发表时间: 2022-03
期刊: Nature reviews. Neurology
影响因子: --
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DOI: 10.1016/j.conb.2020.11.007
发表时间: 2021-06
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