小柯机器人

美国波士顿儿童医院Hisashi Umemori研究组报道了建立功能分离的多巴胺能突触的投射特异性信号。相关论文于2023年8月16日发表在《细胞》杂志上。

通过无偏搜索，他们发现两组拮抗TGF-β家族成员骨形态发生蛋白(BMP)6/BMP2和转化生长因子(TGF)-β2，分别调节黑质纹状体和中边缘神经元的多巴胺能突触发育。它们受体的投射优先表达有助于特定突触的发育。下游、Smad1和Smad2在黑质纹状体和中边缘投射的多巴胺能突触发育和功能中被特异性激活。

值得注意的是，Smad1突变小鼠表现出运动缺陷，而Smad2突变小鼠表现出缺乏动力。这些结果揭示了正确建立功能分离的多巴胺能突触的分子逻辑，并可能提供通过靶向特定的BMP /TGF-β和/或Smads治疗相关的、投射特异性疾病症状的策略。

据介绍，多巴胺能投射调节各种脑功能，并与许多神经精神疾病有关。连接中脑和纹状体的多巴胺能突起有两个在解剖学和功能上都截然不同——控制运动的黑纹状体和调节动机的中脑边缘。然而，这些离散的多巴胺能突触连接是如何建立的尚不清楚。

附：英文原文

Title: The projection-specific signals that establish functionally segregated dopaminergic synapses

Author: Akiko Terauchi, Patricia Yee, Erin M. Johnson-Venkatesh, Mariel P. Seiglie, Lisa Kim, Julia C. Pitino, Eli Kritzer, Qiyu Zhang, Jie Zhou, Yulong Li, David D. Ginty, Wei-Chung A. Lee, Hisashi Umemori

Issue&Volume: 2023-08-16

Abstract: Dopaminergic projections regulate various brain functions and are implicated in manyneuropsychiatric disorders. There are two anatomically and functionally distinct dopaminergicprojections connecting the midbrain to striatum: nigrostriatal, which controls movement,and mesolimbic, which regulates motivation. However, how these discrete dopaminergicsynaptic connections are established is unknown. Through an unbiased search, we identifythat two groups of antagonistic TGF-β family members, bone morphogenetic protein (BMP)6/BMP2and transforming growth factor (TGF)-β2, regulate dopaminergic synapse developmentof nigrostriatal and mesolimbic neurons, respectively. Projection-preferential expressionof their receptors contributes to specific synapse development. Downstream, Smad1and Smad2 are specifically activated and required for dopaminergic synapse developmentand function in nigrostriatal vs. mesolimbic projections. Remarkably, Smad1 mutantmice show motor defects, whereas Smad2 mutant mice show lack of motivation. These results uncover the molecular logic underlying the proper establishment of functionallysegregated dopaminergic synapses and may provide strategies to treat relevant, projection-specificdisease symptoms by targeting specific BMPs/TGF-β and/or Smads.

DOI: 10.1016/j.cell.2023.07.023

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00801-2