Parallel Social Information Processing Circuits Are Differentially Impacted in Autism,Neuron

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Parallel Social Information Processing Circuits Are Differentially Impacted in Autism
Neuron ( IF 16.2 ) Pub Date : 2020-10-27 , DOI: 10.1016/j.neuron.2020.10.002
Eastman M Lewis ₁ , Genevieve L Stein-O'Brien ₂ , Alejandra V Patino ₃ , Romain Nardou ₁ , Cooper D Grossman ₄ , Matthew Brown ₅ , Bidii Bangamwabo ₅ , Ndeye Ndiaye ₅ , Daniel Giovinazzo ₅ , Ian Dardani ₆ , Connie Jiang ₇ , Loyal A Goff ₈ , Gül Dölen ₁

Affiliation

The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Brain Science Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Kavli Neuroscience Discovery Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Wendy Klag Institute for Autism and Developmental Disabilities, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Kavli Neuroscience Discovery Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD 21205; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Brain Science Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Kavli Neuroscience Discovery Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Wendy Klag Institute for Autism and Developmental Disabilities, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Brain Science Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Kavli Neuroscience Discovery Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell and Molecular Biology Group, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; The Kavli Neuroscience Discovery Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.

Parallel processing circuits are thought to dramatically expand the network capabilities of the nervous system. Magnocellular and parvocellular oxytocin neurons have been proposed to subserve two parallel streams of social information processing, which allow a single molecule to encode a diverse array of ethologically distinct behaviors. Here we provide the first comprehensive characterization of magnocellular and parvocellular oxytocin neurons in male mice, validated across anatomical, projection target, electrophysiological, and transcriptional criteria. We next use novel multiple feature selection tools in Fmr1-KO mice to provide direct evidence that normal functioning of the parvocellular but not magnocellular oxytocin pathway is required for autism-relevant social reward behavior. Finally, we demonstrate that autism risk genes are enriched in parvocellular compared with magnocellular oxytocin neurons. Taken together, these results provide the first evidence that oxytocin-pathway-specific pathogenic mechanisms account for social impairments across a broad range of autism etiologies.

中文翻译：

并行社会信息处理回路在自闭症中受到不同的影响

并行处理电路被认为可以极大地扩展神经系统的网络能力。人们提出，大细胞和小细胞催产素神经元可以促进社会信息处理的两个并行流，从而允许单个分子编码多种行为学上不同的行为。在这里，我们提供了雄性小鼠大细胞和小细胞催产素神经元的首次全面表征，并在解剖学、投射目标、电生理学和转录标准方面进行了验证。接下来，我们在Fmr1 -KO 小鼠中使用新颖的多特征选择工具来提供直接证据，证明自闭症相关的社会奖励行为需要小细胞催产素途径的正常功能，而不是大细胞催产素途径的正常功能。最后，我们证明，与大细胞催产素神经元相比，自闭症风险基因在小细胞催产素神经元中富集。总而言之，这些结果提供了第一个证据，证明催产素途径特异性致病机制可以解释多种自闭症病因中的社会障碍。

更新日期：2020-11-26

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